Publications by authors named "Qiulian Zhou"

34 Publications

Exercise downregulates HIPK2 and HIPK2 inhibition protects against myocardial infarction.

EBioMedicine 2021 Dec 24;74:103713. Epub 2021 Nov 24.

Shanghai Engineering Research Center of Organ Repair, Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong), School of Medicine, Shanghai University, Nantong 226011, China; Cardiac Regeneration and Ageing Lab, Institute of Cardiovascular Sciences, School of Life Science, Shanghai University, Shanghai, 200444, China. Electronic address:

Background: Exercise can protect myocardial infarction (MI) and downregulate cardiac Homeodomain-Interacting Protein Kinase 2 (HIPK2). However, the role of HIPK2 in MI is unclear.

Methods: HIPK2 mice and miR-222 rats, HIPK2 inhibitor (PKI1H) and adeno-associated virus serotype 9 (AAV9) carrying miR-222 were applied in the study. Animals were subjected to running, swimming, acute MI or post-MI remodeling. HIPK2 inhibition and P53 activator were used in neonatal rat cardiomyocytes (NRCMs) and human embryonic stem cell-derived cardiomyocytes (hESC-CMs) subjected to oxygen glucose deprivation/reperfusion (OGD/R). Serum miR-222 levels were analyzed in healthy people and MI patients that were survival or readmitted to the hospital and/or died.

Findings: Cardiac HIPK2 protein levels were reduced by exercise while increased in MI. In vitro, HIPK2 suppression by lentiviral vectors or inhibitor prevented apoptosis induced by OGD/R in NRCMs and hESC-CMs. HIPK2 inhibitor-treated mice and HIPK2 mice reduced infarct size after acute MI, and preserved cardiac function in MI remodeling. Mechanistically, protective effect against apoptosis by HIPK2 suppression was reversed by P53 activators. Furthermore, increasing levels of miR-222, targeting HIPK2, protected post-MI cardiac dysfunction, whereas cardiac dysfunction post-MI was aggravated in miR-222 rats. Moreover, serum miR-222 levels were significantly reduced in MI patients, as well as in MI patients that were readmitted to the hospital and/or died compared to those not.

Interpretation: Exercise-induced HIPK2 suppression attenuates cardiomyocytes apoptosis and protects MI by decreasing P-P53. Inhibition of HIPK2 represents a potential novel therapeutic intervention for MI.

Funding: This work was supported by the grants from National Key Research and Development Project (2018YFE0113500 to JJ Xiao), National Natural Science Foundation of China (82020108002, 81722008, and 81911540486 to JJ Xiao, 81400647 to MJ Xu, 81800265 to YJ Liang), Innovation Program of Shanghai Municipal Education Commission (2017-01-07-00-09-E00042 to JJ Xiao), the grant from Science and Technology Commission of Shanghai Municipality (18410722200 and 17010500100 to JJ Xiao), the "Dawn" Program of Shanghai Education Commission (19SG34 to JJ Xiao), Shanghai Sailing Program (21YF1413200 to QL Zhou). JS is supported by Horizon2020 ERC-2016-COG EVICARE (725229).
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http://dx.doi.org/10.1016/j.ebiom.2021.103713DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8626841PMC
December 2021

Non-coding RNA basis of muscle atrophy.

Mol Ther Nucleic Acids 2021 Dec 19;26:1066-1078. Epub 2021 Oct 19.

Institute of Geriatrics (Shanghai University), Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong), School of Medicine, Shanghai University, Nantong 226011, China.

Muscle atrophy is a common complication of many chronic diseases including heart failure, cancer cachexia, aging, etc. Unhealthy habits and usage of hormones such as dexamethasone can also lead to muscle atrophy. However, the underlying mechanisms of muscle atrophy are not completely understood. Non-coding RNAs (ncRNAs), such as microRNAs (miRNAs), long ncRNAs (lncRNAs), and circular RNAs (circRNAs), play vital roles in muscle atrophy. This review mainly discusses the regulation of ncRNAs in muscle atrophy induced by various factors such as heart failure, cancer cachexia, aging, chronic obstructive pulmonary disease (COPD), peripheral nerve injury (PNI), chronic kidney disease (CKD), unhealthy habits, and usage of hormones; highlights the findings of ncRNAs as common regulators in multiple types of muscle atrophy; and summarizes current therapies and underlying mechanisms for muscle atrophy. This review will deepen the understanding of skeletal muscle biology and provide new strategies and insights into gene therapy for muscle atrophy.
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http://dx.doi.org/10.1016/j.omtn.2021.10.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8569427PMC
December 2021

Long Noncoding RNA Cardiac Physiological Hypertrophy-Associated Regulator Induces Cardiac Physiological Hypertrophy and Promotes Functional Recovery After Myocardial Ischemia-Reperfusion Injury.

Circulation 2021 07 21;144(4):303-317. Epub 2021 May 21.

Shanghai Engineering Research Center of Organ Repair, School of Medicine (L.W., Y.B., J.W., Q.Z., J.X.), Shanghai University, China.

Background: The benefits of exercise training in the cardiovascular system have been well accepted; however, the underlying mechanism remains to be explored. Here, we report the initial functional characterization of an exercise-induced cardiac physiological hypertrophy-associated novel long noncoding RNA (lncRNA).

Methods: Using lncRNA microarray profiling, we identified lncRNAs in contributing the modulation of exercise-induced cardiac growth that we termed cardiac physiological hypertrophy-associated regulator (CPhar). Mice with adeno-associated virus serotype 9 driving CPhar overexpression and knockdown were used in in vivo experiments. Swim training was used to induce physiological cardiac hypertrophy in mice, and ischemia reperfusion injury surgery was conducted to investigate the protective effects of CPhar in mice. To investigate the mechanisms of CPhar's function, we performed various analyses including quantitative reverse transcription polymerase chain reaction, Western blot, histology, cardiac function (by echocardiography), functional rescue experiments, mass spectrometry, in vitro RNA transcription, RNA pulldown, RNA immunoprecipitation, chromatin immunoprecipitation assay, luciferase reporter assay, and coimmunoprecipitation assays.

Results: We screened the lncRNAs in contributing the modulation of exercise-induced cardiac growth through lncRNA microarray profiling and found that CPhar was increased with exercise and was necessary for exercise-induced physiological cardiac growth. The gain and loss of function of CPhar regulated the expression of proliferation markers, hypertrophy, and apoptosis in cultured neonatal mouse cardiomyocytes. Overexpression of CPhar prevented myocardial ischemia reperfusion injury and cardiac dysfunction in vivo. We identified DDX17 (DEAD-Box Helicase 17) as a binding partner of CPhar in regulating CPhar downstream factor ATF7 (activating transcription factor 7) by sequestering C/EBPβ (CCAAT/enhancer binding protein beta).

Conclusions: Our study of this lncRNA CPhar provides new insights into the regulation of exercise-induced cardiac physiological growth, demonstrating the cardioprotective role of CPhar in the heart, and expanding our mechanistic understanding of lncRNA function, as well.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.120.050446DOI Listing
July 2021

The anti-microbial peptide LL-37/CRAMP levels are associated with acute heart failure and can attenuate cardiac dysfunction in multiple preclinical models of heart failure.

Theranostics 2020 15;10(14):6167-6181. Epub 2020 May 15.

Cardiac Regeneration and Ageing Lab, Institute of Cardiovascular Sciences, School of Life Science, Shanghai University, Shanghai 200444, China.

: Biomarkers for the diagnosis of heart failure (HF) are clinically essential. Circulating antimicrobial peptides LL-37 has emerged as a novel biomarker in cardiovascular disease, however, its relevance as a biomarker for acute HF are undetermined. : Acute HF patients were enrolled in this study and the serum levels of LL-37/CRAMP (cathelicidin-related antimicrobial peptide) were measured by ELISA. The receiver-operator characteristic (ROC) curve was used to determine if serum LL-37 could be a biomarker for acute HF. Mouse CRAMP (mCRAMP, mouse homolog for human LL-37) was also determined in both heart and serum samples of, transverse aortic constriction (TAC)- and isoproterenol (ISO)-induced HF mice models, and phenylephrine (PE) and angiotensin II (AngII)-induced neonatal mouse cardiomyocytes (NMCMs) hypertrophic models, both intracellular and secreted, by ELISA. The protective effects of mCRAMP were determined in TAC, ISO, and AngII-induced HF in mice while whether HF was exacerbated in AngII-infused animals were checked in mCRAMP knockout mice. The underlying mechanism for protective effects of CARMP in pathological hypertrophy was determined by using a NF-κB agonist together with rCRAMP (rat homolog for human LL-37) in AngII or PE treated neonatal rat cardiomyocytes (NRCMs). : Serum levels of LL-37 were significantly decreased in acute HF patients (area under the curve (AUC) of 0.616), and negatively correlated with NT-proBNP. We further confirmed that mCRAMP was decreased in both heart and serum samples of TAC- and ISO-induced HF mice models. Moreover, in PE and AngII-induced NMCMs hypertrophic models, both intracellular and secreted mCRAMP levels were reduced. Functionally, mCRAMP could attenuate TAC, ISO, and AngII-induced HF in mice while CRAMP deficiency exacerbated HF. Mechanistically, the anti-hypertrophy effects of CRAMP were mediated by NF-κB signaling. : Collectively, serum LL-37 is associated with acute HF and increasing CRAMP is protective against deleterious NF-κB signaling in the rodent.
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http://dx.doi.org/10.7150/thno.46225DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7255020PMC
May 2021

Circulating microRNAs in Response to Exercise Training in Healthy Adults.

Front Genet 2020 18;11:256. Epub 2020 Mar 18.

Cardiac Regeneration and Ageing Lab, Institute of Cardiovascular Sciences, School of Life Sciences, Shanghai University, Shanghai, China.

Circulating microRNAs (miRNAs, miRs) have great potential as cardiac biomarkers and they are also being explored for their roles in intercellular communication and gene expression regulation. The analysis of circulating miRNAs in response to exercise would provide a deeper understanding of the molecular response to physical activity and valuable information for clinical practice. Here, eight male college students were recruited to participate in cardiopulmonary exercise testing (CPET) and 1 h acute exercise training (AET). Blood samples were collected and serum miRNAs involved in angiogenesis, inflammation and enriched in muscle and/or cardiac tissues were analyzed before and after cardiopulmonary exercise and acute exercise. The miRNAs we detected were miR-1, miR-20a, miR-21, miR-126, miR-133a, miR-133b, miR-146, miR155, miR-208a, miR-208b, miR-210, miR-221, miR-222, miR-328, miR-378, miR-499, and miR-940. We found that serum miR-20a was decreased significantly after CPET and serum miR-21 was increased after AET. In addition, no robust correlation was identified between the changes of these miRNAs and makers of cardiac function and exercise capacity, which indicates a distinct adaptation of these miRNAs to exercise. Future studies are highly needed to define the potential use of these circulating miRNAs as useful biomarkers of exercise training, and disclose the biological function of circulating miRNAs as physiological mediators of exercise-induced cardiovascular adaptation.
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http://dx.doi.org/10.3389/fgene.2020.00256DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7093586PMC
March 2020

Editorial: Gender Differences in Cardiovascular Diseases.

J Cardiovasc Transl Res 2020 02;13(1):1-2

Cardiac Regeneration and Ageing Lab, Institute of Cardiovascular Sciences, School of Life Science, Shanghai University, 333 Nan Chen Road, Shanghai, 200444, China.

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http://dx.doi.org/10.1007/s12265-020-09956-9DOI Listing
February 2020

Cathelicidin-related antimicrobial peptide protects against myocardial ischemia/reperfusion injury.

BMC Med 2019 02 20;17(1):42. Epub 2019 Feb 20.

Cardiac Regeneration and Ageing Lab, Institute of Cardiovascular Sciences, School of Life Science, Shanghai University, 333 Nan Chen Road, Shanghai, 200444, China.

Background: Cathelicidins are a major group of natural antimicrobial peptides which play essential roles in regulating host defense and immunity. In addition to the antimicrobial and immunomodulatory activities, recent studies have reported the involvement of cathelicidins in cardiovascular diseases by regulating inflammatory response and microvascular dysfunction. However, the role of cathelicidins in myocardial apoptosis upon cardiac ischemia/reperfusion (I/R) injury remains largely unknown.

Methods: CRAMP (cathelicidin-related antimicrobial peptide) levels were measured in the heart and serum from I/R mice and in neonatal mouse cardiomyocytes treated with oxygen glucose deprivation/reperfusion (OGDR). Human serum cathelicidin antimicrobial peptide (LL-37) levels were measured in myocardial infarction (MI) patients. The role of CRAMP in myocardial apoptosis upon I/R injury was investigated in mice injected with the CRAMP peptide and in CRAMP knockout (KO) mice, as well as in OGDR-treated cardiomyocytes.

Results: We observed reduced CRAMP level in both heart and serum samples from I/R mice and in OGDR-treated cardiomyocytes, as well as reduced LL-37 level in MI patients. Knockdown of CRAMP enhanced cardiomyocyte apoptosis, and CRAMP KO mice displayed increased infarct size and myocardial apoptosis. In contrast, the CRAMP peptide reduced cardiomyocyte apoptosis and I/R injury. The CRAMP peptide inhibited cardiomyocyte apoptosis by activation of Akt and ERK1/2 and phosphorylation and nuclear export of FoxO3a. c-Jun was identified as a negative regulator of the CRAMP gene. Moreover, lower level of serum LL-37/neutrophil ratio was associated with readmission and/or death in MI patients during 1-year follow-up.

Conclusions: CRAMP protects against cardiomyocyte apoptosis and cardiac I/R injury via activation of Akt and ERK and phosphorylation and nuclear export of FoxO3a. Increasing LL-37 might be a novel therapy for cardiac ischemic injury.
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http://dx.doi.org/10.1186/s12916-019-1268-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6381635PMC
February 2019

Noncoding RNAs in Muscle Atrophy.

Adv Exp Med Biol 2018;1088:249-266

Cardiac Regeneration and Ageing Lab, Institute of Cardiovascular Sciences, School of Life Science, Shanghai University, Shanghai, China.

Denervation, disuse, fasting, and various diseases could induce skeletal muscle atrophy, which results in the decline of life quality and increase of the mortality risk for patients. Noncoding RNAs (ncRNAs) are implicated important in regulating gene expression. Thus, ncRNAs, especially microRNAs and long noncoding RNAs (lncRNAs), have gained widespread attention as crucial players in numerous physiological and pathological processes, including skeletal muscle atrophy. In this review, we comprehensively described the potential of circulating microRNAs as biomarkers, summarized the profiling of microRNAs and lncRNAs in atrophying muscles, as well as discussed the effects and underlying mechanisms of microRNA machinery proteins, microRNAs, and lncRNAs in skeletal muscle atrophy. Considering the large quantity and variety of ncRNAs, the understanding of ncRNAs in muscle atrophy is still very limited. Future studies are needed to elucidate the possibility of ncRNAs as diagnosis biomarkers and therapeutic targets in muscle atrophy.
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http://dx.doi.org/10.1007/978-981-13-1435-3_11DOI Listing
July 2019

Circular RNAs as Potential Theranostics in the Cardiovascular System.

Mol Ther Nucleic Acids 2018 Dec 2;13:407-418. Epub 2018 Oct 2.

Cardiac Regeneration and Ageing Lab, Institute of Cardiovascular Sciences, School of Life Science, Shanghai University, Shanghai 200444, China. Electronic address:

Cardiovascular diseases (CVDs) represent the largest contributor to mortality worldwide. Identification of novel therapeutic targets and biomarkers for CVDs is urgently needed. Circular RNAs (circRNAs) are endogenous, abundant, and stable non-coding RNAs formed by back-splicing events. Their role as regulators of gene expression has been increasingly reported. Notably, circRNAs mediate essential physiological and pathological processes in the cardiovascular system. Our first aim, therefore, is to summarize recent advances in the role of circRNAs in cardiac development as well as in pathogenesis of various CVDs. Because circRNAs are stable in circulation and their dynamic changes may reflect different disease stages, they are considered ideal biomarkers. Therefore, our second aim is to review studies that have identified circulating circRNAs as biomarkers for CVDs. Finally, we discuss the shortage of functional studies and the limitations of available clinical studies and provide future perspectives.
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http://dx.doi.org/10.1016/j.omtn.2018.09.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6205062PMC
December 2018

Circular RNAs in Cardiovascular Diseases.

Adv Exp Med Biol 2018;1087:191-204

School of Life Science, Institute of Cardiovascular Sciences, Shanghai University, Shanghai, China.

Circular RNAs (circRNAs), a group of circular RNA molecules with a 3',5'-phosphodiester bond at the junction site, are generated by back-splicing of precursor mRNAs. Most of the circular RNAs originate from the exon region of the encoded protein, and some are derived from intron regions, antisense transcripts, or long noncoding RNAs. Circular RNAs are abundantly in eukaryotic transcriptome and participate in various biological processes. It is closely associated with various diseases such as tumors, diabetes, nervous system diseases, and cardiovascular diseases. In cardiovascular system, numerous circRNAs have been identified and involved in important processes of cardiovascular development and diseases. Here we will review the latest research progress of circular RNA in cardiovascular diseases. Also, we will outline the specific examples of circRNAs involved in cardiovascular system regulatory effects, including act as miRNA sponges, interaction with RNA-binding proteins, regulated by RNA-binding proteins and serve as biomarkers. In addition, potential mechanisms underlying the regulatory role of circRNAs in cardiovascular diseases will be discussed.
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http://dx.doi.org/10.1007/978-981-13-1426-1_15DOI Listing
February 2019

Circular RNAs as Novel Biomarkers for Cardiovascular Diseases.

Adv Exp Med Biol 2018;1087:159-170

Cardiac Regeneration and Ageing Lab, Institute of Cardiovascular Sciences, School of Life Science, Shanghai University, Shanghai, China.

Cardiovascular diseases are among the most serious diseases, which are a leading cause of death across the world. Early diagnosis and prognosis prediction are keys for treatment and reduction of death rates. Circular RNAs (circRNAs) play a critical role in the physiology and pathology of biological system and participate in the development of diseases. In addition, circRNAs are relative stable and abundant. Therefore, many studies have suggested that circRNAs could be used as biomarkers for diseases, such as neurological diseases, cancers, immune diseases, and digestive diseases. Here we summarize recent studies on circRNAs and compare the characteristics of circRNAs with traditional biomarkers. Finally, we highlight the value of circRNAs as potential biomarkers for cardiovascular diseases, including acute myocardial infarction, heart failure, coronary artery disease, and hypertension. In conclusion, circRNAs may be promising biomarkers for cardiovascular diseases.
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http://dx.doi.org/10.1007/978-981-13-1426-1_13DOI Listing
February 2019

miR-486 inhibits PM2.5-induced apoptosis and oxidative stress in human lung alveolar epithelial A549 cells.

Ann Transl Med 2018 Jun;6(11):209

Shanghai Applied Radiation Institute, School of Environmental and Chemical Engineering, Shanghai University, Shanghai 200444, China.

Background: Environmental exposure to particulate matter 2.5 (PM2.5) threatens public health, which has caused worldwide concerns. MicroRNAs (miRNAs, miRs) participate in multiple biological regulation. Among them, miR-486 has been reported to be a beneficial molecule for cell survival in various cell types. However, the potential function of miR-486 in PM2.5-induced cytotoxic is still uncertain.

Methods: The expression of miR-486 was detected by quantitative real-time polymerase chain reaction (qRT-PCR) after A549 cells incubated with PM2.5. Then TUNEL staining and DCFH-DA fluorescence were used to test the apoptosis and ROS generation of A549 cells after exposed to PM2.5 with miR-486 mimic. Western blot was performed to determine the expression of Bax/Bcl2 ratio. In addition, western blot and rescue experiments were conducted to determine the target gene of miR-486.

Results: After treated with PM2.5, the expression of miR-486 was decreased. And miR-486 mimic treatment reduced cell apoptosis and reactive oxygen species (ROS) generation induced by PM2.5 exposure. Further studies showed that miR-486 negatively regulated the protein levels of PTEN and FOXO1. Rescue experiments demonstrated that PTEN and FOXO1 mediated the protective effects of miR-486 in PM2.5-treated human lung alveolar epithelial A549 cells.

Conclusions: Collectively, our findings identify that miR-486 relieves PM2.5-induced cell injury by targeting PTEN and FOXO1 in human lung alveolar epithelial A549 cells.
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http://dx.doi.org/10.21037/atm.2018.06.09DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6035978PMC
June 2018

Dynamic Regulation of Circulating microRNAs During Acute Exercise and Long-Term Exercise Training in Basketball Athletes.

Front Physiol 2018 26;9:282. Epub 2018 Mar 26.

Cardiac Regeneration and Ageing Lab, School of Life Science, Shanghai University, Shanghai, China.

Emerging evidence indicates the beneficial effects of physical exercise on human health, which depends on the intensity, training time, exercise type, environmental factors, and the personal health status. Conventional biomarkers provide limited insight into the exercise-induced adaptive processes. Circulating microRNAs (miRNAs, miRs) are dynamically regulated in response to acute exhaustive exercise and sustained rowing, running and cycling exercises. However, circulating miRNAs in response to long-term basketball exercise remains unknown. Here, we enrolled 10 basketball athletes who will attend a basketball season for 3 months. Specifically, circulating miRNAs which were involved in angiogenesis, inflammation and enriched in muscle and/or cardiac tissues were analyzed at baseline, immediately following acute exhaustive exercise and after 3-month basketball matches in competitive male basketball athletes. Circulating miR-208b was decreased and miR-221 was increased after 3-month basketball exercise, while circulating miR-221, miR-21, miR-146a, and miR-210 were reduced at post-acute exercise. The change of miR-146a (baseline vs. post-acute exercise) showed linear correlations with baseline levels of cardiac marker CKMB and the changes of inflammation marker Hs-CRP (baseline vs. post-acute exercise). Besides, linear correlation was observed between miR-208b changes (baseline vs. after long-term exercise) and AT VO (baseline). The changes of miR-221 (baseline vs. after long-term exercise) were significantly correlated with AT VO, peak work load and CK (after 3-month basketball matches). Although further studies are needed, present findings set the stage for defining circulating miRNAs as biomarkers and suggesting their physiological roles in long-term exercise training induced cardiovascular adaptation.
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http://dx.doi.org/10.3389/fphys.2018.00282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5890107PMC
March 2018

SGK1 inhibits PM2.5-induced apoptosis and oxidative stress in human lung alveolar epithelial A549 cells.

Biochem Biophys Res Commun 2018 02 3;496(4):1291-1295. Epub 2018 Feb 3.

Shanghai Applied Radiation Institute, School of Environmental and Chemical Engineering, Shanghai University, Shanghai, China. Electronic address:

Emerging evidence demonstrated that particulate matter 2.5 (PM2.5) is an important environmental risk factor for lung diseases. Serum- and glucocorticoid-inducible kinase 1(SGK1) was reported to be a crucial factor for cell survival. However, the role of SGK1 in PM2.5-induced cell injury is still unclear. In this work, we firstly found that the expression of SGK1 was decreased in PM2.5-treated human lung alveolar epithelial (A549) cells by western blot. In addition, overexpression of SGK1 significantly attenuated A549 cell apoptosis and reduced the reactive oxygen species (ROS) generation induced by PM2.5. Moreover, we found that PM2.5 exposure significantly promoted the ERK1/2 activation and inhibited the AKT activation, whereas overexpression of SGK1 could reverse that. Finally, the results of the rescue experiment showed that MK2206 (AKT inhibitor) could rescue the impact of SGK1 on A549 cell apoptosis, while PD98059 (ERK1/2 inhibitor) could not further aggravate the impact. Taken together, our results suggest that SGK1 inhibits PM2.5-induced cell apoptosis and ROS generation via ERK1/2 and AKT signaling pathway in human lung alveolar epithelial A549 cells.
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http://dx.doi.org/10.1016/j.bbrc.2018.02.002DOI Listing
February 2018

miR-21 suppression prevents cardiac alterations induced by d-galactose and doxorubicin.

J Mol Cell Cardiol 2018 02 9;115:130-141. Epub 2018 Jan 9.

Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China. Electronic address:

d-galactose (d-gal)-induced cardiac alterations and Doxorubicin (Dox)-induced cardiomyocyte senescence are commonly used models to study cardiac aging. Accumulating evidence has suggested that microRNAs (miRNAs, miRs) are critically involved in the regulation of cellular and organismal aging and age-related diseases. However, little has been revealed about the roles of miRNAs in cardiac alterations induced by d-gal and Dox. In this study, we used miRNA arrays to investigate the dysregulated miRNAs in heart samples from 15month-old versus 2month-old male C57BL/6 mice and further validated them in d-gal-induced pseudo-aging mouse model and Dox-induced cardiomyocyte senescence in vitro model. We confirmed a significant increase of miR-21 in all these models by quantitative reverse transcription polymerase chain reactions. We further demonstrated that miR-21 was able to promote Dox-induced cardiomyocyte senescence whereas suppression of miR-21 could prevent that, as determined by percentage of β-gal-positive cells and gene markers of aging. Phosphatase and tensin homolog (PTEN) was identified as a target gene of miR-21, mediating its effect in increasing cardiomyocyte senescence. Finally, we found that miR-21 knockout mice were resistant to d-gal-induced alterations in aging-markers and cardiac function. Collectively, this study provides direct evidence that inhibition of miR-21 is protective against d-gal-induced cardiac alterations and Dox-induced cardiomyocyte senescence via targeting PTEN. Inhibition of miR-21 might be a novel strategy to combat cardiac aging.
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http://dx.doi.org/10.1016/j.yjmcc.2018.01.007DOI Listing
February 2018

Therapeutic Inhibition of miR-4260 Suppresses Colorectal Cancer via Targeting MCC and SMAD4.

Theranostics 2017 10;7(7):1901-1913. Epub 2017 Apr 10.

Department of General Surgery, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China.

Dysregulation of microRNAs (miRNAs, miRs) and their putative target genes have been increasingly reported to contribute to colorectal cancer. However, miRNAs that directly target the mutated in colorectal cancer (MCC) gene, a tumor suppressor which is downregulated or inactivated in colorectal cancer, remain largely unknown. By using an array-based miRNA analysis, we identified a group of miRNAs that were dysregulated in human metastatic non-metastatic colorectal cancer tissues. One of these miRNAs, miR-4260, was predicted to target MCC in the miRDB database. Results using human HCT116 and HT29 colorectal cancer cell lines showed that miR-4260 mimic enhanced cell proliferation and migration and reduced apoptosis induced by the chemotherapeutic agent 5-fluorouracil while miR-4260 inhibitor had inverse effects. Furthermore, miR-4260 negatively regulated MCC as well as SMAD4 by directly binding to the 3'untranslational region (3'UTR). Using siRNAs targeting MCC or SMAD4, we showed that upregulation of MCC and SMAD4 was essential to mediate the functional roles of miR-4260 inhibitor in colorectal cancer cells. Our experiments indicated that inhibition of miR-4260 reduced colorectal tumor growth in nude mice subcutaneously implanted with HCT116 cells. Significantly, miR-4260 was increased in human colorectal cancer tissues with simultaneous downregulation of MCC and SMAD4, strongly suggesting the clinical relevance of targeting miR-4260 in the treatment of colorectal cancer. In summary, we identified miR-4260 as a novel oncomiR for colorectal cancer that targets MCC and SMAD4. Inhibition of miR-4260 can, therefore, be a potential therapeutic strategy for colorectal cancer.
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http://dx.doi.org/10.7150/thno.19168DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5479277PMC
March 2018

miR-29b contributes to multiple types of muscle atrophy.

Nat Commun 2017 05 25;8:15201. Epub 2017 May 25.

Cardiac Regeneration and Ageing Lab, School of Life Science, Shanghai University, Shanghai 200444, China.

A number of microRNAs (miRNAs, miRs) have been shown to play a role in skeletal muscle atrophy, but their role is not completely understood. Here we show that miR-29b promotes skeletal muscle atrophy in response to different atrophic stimuli in cells and in mouse models. miR-29b promotes atrophy of myotubes differentiated from C2C12 or primary myoblasts, and conversely, its inhibition attenuates atrophy induced by dexamethasone (Dex), TNF-α and HO treatment. Targeting of IGF-1 and PI3K(p85α) by miR-29b is required for induction of muscle atrophy. In vivo, miR-29b overexpression is sufficient to promote muscle atrophy while inhibition of miR-29b attenuates atrophy induced by denervation and immobilization. These data suggest that miR-29b contributes to multiple types of muscle atrophy via targeting of IGF-1 and PI3K(p85α), and that suppression of miR-29b may represent a therapeutic approach for muscle atrophy induced by different stimuli.
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http://dx.doi.org/10.1038/ncomms15201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5458521PMC
May 2017

Traditional Chinese Medication Qiliqiangxin Protects Against Cardiac Remodeling and Dysfunction in Spontaneously Hypertensive Rats.

Int J Med Sci 2017 9;14(5):506-514. Epub 2017 Apr 9.

Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.

Qiliqiangxin (QLQX), a traditional Chinese herbs medication, exerted protective effect in chronic heart failure patients in a multicenter randomized double-blind study. QLQX has also been found to improve cardiac function and reduce cardiac fibrosis in spontaneously hypertension animal model. However, the effect of longterm treatment with QLQX in such a condition and the related molecular mechanisms remain largely unknown. In the present study, thirteen-week-old spontaneously hypertensive rats (SHRs) were treated by daily intragastric administration of QLQX or saline for one year. Echocardiography, electron microscopy, and Masson's trichrome staining were used to determine cardiac function, mitochondria ultrastructure, and cardiac fibrosis, respectively. Quantitative reverse transcription polymerase chain reactions (qRT-PCRs) and Western blotting were used to determine gene expressions. We found that QLQX significantly improved cardiac function and reduced gene markers of pathological hypertrophy including ANP, BNP, and Myh7. QLQX also attenuated cardiac fibrosis and apoptosis in SHRs as evidenced by downregulation of α-SMA, collagen I, collagen III, and TGF-β expressions and reduction of Bax to Bcl-2 ratio. Moreover, the damage of mitochondrial ultrastructure was greatly improved and the reduction of PPAR-α, PPAR-γ, and PGC-1α expression levels was significantly restored in SHRs by treatment with QLQX. In conclusion, longterm treatment with QLQX protects against cardiac remodeling and dysfunction in hypertension by increasing PPARs and PGC-1α.
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http://dx.doi.org/10.7150/ijms.18142DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5441043PMC
March 2018

MicroRNA Expression Signature in Human Calcific Aortic Valve Disease.

Biomed Res Int 2017 11;2017:4820275. Epub 2017 Apr 11.

Cardiac Regeneration and Ageing Lab, School of Life Science, Shanghai University, Shanghai 200444, China.

Altered microRNA (miRNA, miR) expression has been related to many disease processes; however, the miRNA expression signature in calcific aortic valve disease (CAVD) is unclear. In this study, microarrays were used to determine the miRNA expression signature of tissue samples from healthy individuals ( = 4) and patients with CAVD ( = 4). TargetScan, PITA, and microRNAorg 3-way databases were used to predict the potential target genes. DIANA-miRPath was used to incorporate the aberrant miRNAs into gene pathways. miRNA microarrays identified 92 differentially expressed miRNAs in CAVD tissues. The principal component analysis (PCA) of these samples and the unsupervised hierarchical clustering analysis based on the 92 aberrantly expressed miRNAs noted that miRNA expression could be categorized into two well-defined clusters that corresponded to healthy control and CAVD. Bioinformatic analysis showed the miRNA targets and potential molecular pathways. Collectively, our study reported the miRNA expression signature in CAVD and may provide potential therapeutic targets for CAVD.
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http://dx.doi.org/10.1155/2017/4820275DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5405367PMC
February 2018

Cardiac cell proliferation is not necessary for exercise-induced cardiac growth but required for its protection against ischaemia/reperfusion injury.

J Cell Mol Med 2017 08 17;21(8):1648-1655. Epub 2017 Mar 17.

Cardiac Regeneration and Ageing Lab, School of Life Science, Shanghai University, Shanghai, China.

The adult heart retains a limited ability to regenerate in response to injury. Although exercise can reduce cardiac ischaemia/reperfusion (I/R) injury, the relative contribution of cardiac cell proliferation including newly formed cardiomyocytes remains unclear. A 4-week swimming murine model was utilized to induce cardiac physiological growth. Simultaneously, the antineoplastic agent 5-fluorouracil (5-FU), which acts during the S phase of the cell cycle, was given to mice via intraperitoneal injections. Using EdU and Ki-67 immunolabelling, we showed that exercise-induced cardiac cell proliferation was blunted by 5-FU. In addition, the growth of heart in size and weight upon exercise was unaltered, probably due to the fact that exercise-induced cardiomyocyte hypertrophy was not influenced by 5-FU as demonstrated by wheat germ agglutinin staining. Meanwhile, the markers for pathological hypertrophy, including ANP and BNP, were not changed by either exercise or 5-FU, indicating that physiological growth still developed in the presence of 5-FU. Furthermore, we showed that CITED4, a key regulator for cardiomyocyte proliferation, was blocked by 5-FU. Meanwhile, C/EBPβ, a transcription factor responsible for both cellular proliferation and hypertrophy, was not altered by treatment with 5-FU. Importantly, the effects of exercise in reducing cardiac I/R injury could be abolished when cardiac cell proliferation was attenuated in mice treated with 5-FU. In conclusion, cardiac cell proliferation is not necessary for exercise-induced cardiac physiological growth, but it is required for exercise-associated protection against I/R injury.
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http://dx.doi.org/10.1111/jcmm.13078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5542911PMC
August 2017

Circulating miR-30d Predicts Survival in Patients with Acute Heart Failure.

Cell Physiol Biochem 2017 16;41(3):865-874. Epub 2017 Feb 16.

Background/aims: Identification of novel biomarkers to identify acute heart failure (AHF) patients at high risk of mortality is an area of unmet clinical need. Recently, we reported that the baseline level of circulating miR-30d was associated with left ventricular remodeling in response to cardiac resynchronization therapy in advanced chronic heart failure patients. However, the role of circulating miR-30d as a prognostic marker of survival in patients with AHF has not been explored.

Methods: Patients clinically diagnosed with AHF were enrolled and followed up for 1 year. Quantitative reverse transcription polymerase chain reactions were used to determine serum miR-30d levels. The univariate logistic regression analysis and multivariate logistic regression analysis were used to determine the predictors for all-cause mortality in AHF patients. Kaplan-Meier survival analysis was used to analyze the role of miR-30d in prediction of survival.

Results: A total of 96 AHF patients were enrolled and followed up for 1 year. Serum miR-30d was significantly lower in AHF patients who expired in the one year follow-up period compared to those who survived. Univariate logistic regression analysis yielded 18 variables that were associated with all-cause mortality in AHF patients, while the multivariate logistic regression analysis identified 4 variables including heart rate, hemoglobin, serum sodium, and serum miR-30d level associated with mortality. ROC curve analysis showed that hemoglobin, heart rate and serum sodium displayed poor prognostic value for AHF (AUCs not higher than 0.700) compared to miR-30d level (AUC = 0.806). Kaplan-Meier survival analysis confirmed that patients with higher serum miR-30d levels had significantly lower mortality (P=0.001).

Conclusion: In conclusion, this study shows evidence for the predictive value of circulating miR-30d as 1-year all-cause mortality in AHF patients. Large multicentre studies are further needed to validate our findings and accelerate the transition to clinical utilization.
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http://dx.doi.org/10.1159/000459899DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5509048PMC
June 2017

Inhibition of miR-155 Protects Against LPS-induced Cardiac Dysfunction and Apoptosis in Mice.

Mol Ther Nucleic Acids 2016 Oct 11;5(10):e374. Epub 2016 Oct 11.

Cardiac Regeneration and Ageing Lab, Experimental Center of Life Sciences, School of Life Science, Shanghai University, Shanghai, China.

Sepsis-induced myocardial dysfunction represents a major cause of death in intensive care units. Dysregulated microRNAs (miR)-155 has been implicated in multiple cardiovascular diseases and miR-155 can be induced by lipopolysaccharide (LPS). However, the role of miR-155 in LPS-induced cardiac dysfunction is unclear. Septic cardiac dysfunction in mice was induced by intraperitoneal injection of LPS (5 mg/kg) and miR-155 was found to be significantly increased in heart challenged with LPS. Pharmacological inhibition of miR-155 using antagomiR improved cardiac function and suppressed cardiac apoptosis induced by LPS in mice as determined by echocardiography, terminal deoxynucleotidyl transferase nick-end labeling (TUNEL) assay, and Western blot for Bax and Bcl-2, while overexpression of miR-155 using agomiR had inverse effects. Pea15a was identified as a target gene of miR-155, mediating its effects in controlling apoptosis of cardiomyocytes as evidenced by luciferase reporter assays, quantitative real time-polymerase chain reaction, Western blot, and TUNEL staining. Noteworthy, miR-155 was also found to be upregulated in the plasma of patients with septic cardiac dysfunction compared to sepsis patients without cardiac dysfunction, indicating a potential clinical relevance of miR-155. The receiver-operator characteristic curve indicated that plasma miR-155 might be a biomarker for sepsis patients developing cardiac dysfunction. Therefore, inhibition of miR-155 represents a novel therapy for septic myocardial dysfunction.
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http://dx.doi.org/10.1038/mtna.2016.80DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5095684PMC
October 2016

Qiliqiangxin Attenuates Phenylephrine-Induced Cardiac Hypertrophy through Downregulation of MiR-199a-5p.

Cell Physiol Biochem 2016 9;38(5):1743-51. Epub 2016 May 9.

Background/aims: Qiliqiangxin (QL), a traditional Chinese medicine, has long been used to treat chronic heart failure. Previous studies demonstrated that QL could prevent cardiac remodeling and hypertrophy in response to hypertensive or ischemic stress. However, little is known about whether QL could modulate cardiac hypertrophy in vitro, and (if so) whether it is through modulation of specific hypertrophy-related microRNA.

Methods: The primary neonatal rat ventricular cardiomyocytes were isolated, cultured, and treated with phenylephrine (PE, 50 µmol/L, 48 h) to induce hypertrophy in vitro, in the presence or absence of pretreatment with QL (0.5 µg/ml, 48 h). The cell surface area was determined by immunofluorescent staining for α-actinin. The mRNA levels of hypertrophic markers including atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and β-myosin heavy chain (MYH7) were assayed by qRT-PCRs. The protein synthesis of cardiomyocytes was determined by the protein/DNA ratio. The miR-199a-5p expression level was quantified in PE-treated cardiomyocytes and heart samples from acute myocardial infarction (AMI) mouse model. MiR-199a-5p overexpression was used to determine its role in the anti-hypertrophic effect of QL on cardiomyocytes.

Results: PE induced obvious enlargement of cell surface in cardiomyocytes, paralleling with increased ANP, BNP, and MYH7 mRNA levels and elevated protein/DNA ratio. All these changes were reversed by the treatment with QL. Meanwhile, miR-199a-5p was increased in AMI mouse heart tissues. Of note, the increase of miR-199a-5p in PE-treated cardiomyocytes was reversed by the treatment with QL. Moreover, overexpression of miR-199a-5p abolished the anti-hypertrophic effect of QL on cardiomyocytes.

Conclusion: QL prevents PE-induced cardiac hypertrophy. MiR-199a-5p is increased in cardiac hypertrophy, while reduced by treatment with QL. miR-199a-5p suppression is essential for the anti-hypertrophic effect of QL on cardiomyocytes.
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http://dx.doi.org/10.1159/000443113DOI Listing
February 2017

miR-19b controls cardiac fibroblast proliferation and migration.

J Cell Mol Med 2016 06 6;20(6):1191-7. Epub 2016 Apr 6.

Department of Thoracic and Cardiovascular Surgery, The Second Affiliated Hospital of NanTong University, Nantong, China.

Cardiac fibrosis is a fundamental constituent of a variety of cardiac dysfunction, making it a leading cause of death worldwide. However, no effective treatment for cardiac fibrosis is available. Therefore, novel therapeutics for cardiac fibrosis are highly needed. Recently, miR-19b has been found to be able to protect hydrogen peroxide (H2 O2 )-induced apoptosis and improve cell survival in H9C2 cardiomyocytes, while down-regulation of miR-19b had opposite effects, indicating that increasing miR-19b may be a new therapeutic strategy for attenuating cellular apoptosis during myocardial ischaemia-reperfusion injury. However, considering the fact that microRNAs might exert a cell-specific role, it is highly interesting to determine the role of miR-19b in cardiac fibroblasts. Here, we found that miR-19b was able to promote cardiac fibroblast proliferation and migration. However, miR-19b mimics and inhibitors did not modulate the expression level of collagen I. Pten was identified as a target gene of miR-19b, which was responsible for the effect of miR-19b in controlling cardiac fibroblast proliferation and migration. Our data suggest that the role of miR-19b is cell specific, and systemic miR-19b targeting in cardiac remodelling might be problematic. Therefore, it is highly needed and also urgent to investigate the role of miR-19b in cardiac remodelling in vivo.
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http://dx.doi.org/10.1111/jcmm.12858DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4882982PMC
June 2016

Telocytes in cardiac regeneration and repair.

Semin Cell Dev Biol 2016 07 28;55:14-21. Epub 2016 Jan 28.

Regeneration and Aging Lab, Experimental Center of Life Sciences, School of Life Science, Shanghai University, Shanghai 200444, China; Shanghai Key Laboratory of Bio-Energy Crops, School of Life Science, Shanghai University, Shanghai 200444, China. Electronic address:

Telocytes (TCs) are a novel type of stromal cells reported by Popescu's group in 2010. The unique feature that distinguishes TCs from other "classical" stromal cells is their extremely long and thin telopodes (Tps). As evidenced by electron microscopy, TCs are widely distributed in almost all tissues and organs. TCs contribute to form a three-dimensional interstitial network and play as active regulators in intercellular communication via homocellular/heterocellular junctions or shed vesicles. Interestingly, increasing evidence suggests the potential role of TCs in regenerative medicine. Although the heart retains some limited endogenous regenerative capacity, cardiac regenerative and repair response is however insufficient to make up the loss of cardiomyocytes upon injury. Developing novel strategies to increase cardiomyocyte renewal and repair is of great importance for the treatment of cardiac diseases. In this review, we focus on the role of TCs in cardiac regeneration and repair. We particularly describe the intercellular communication between TCs and cardiomyocytes, stem/progenitor cells, endothelial cells, and fibroblasts. Also, we discuss the current knowledge about TCs in cardiac repair after myocardial injury, as well as their potential roles in cardiac development and aging. TC-based therapy or TC-derived exosome delivery might be used as novel therapeutic strategies to promote cardiac regeneration and repair.
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http://dx.doi.org/10.1016/j.semcdb.2016.01.037DOI Listing
July 2016

Circulating miR-21, miR-378, and miR-940 increase in response to an acute exhaustive exercise in chronic heart failure patients.

Oncotarget 2016 Mar;7(11):12414-25

Regeneration and Ageing Lab, Experimental Center of Life Sciences, School of Life Science, Shanghai University, Shanghai 200444, China.

Congestive heart failure (CHF) is a major cause of hospitalizations, morbidity, and mortality in Western societies. In addition to optimal medical and device therapy, exercise training is an important adjunct treatment option for CHF patients. MicroRNAs (miRNAs, miRs) participate in a variety of physiological and pathological processes. Dynamic regulation of circulating miRNAs during exercise in healthy persons and athletes has recently been documented, however, the response of circulating miRNAs to exercise in CHF patients is undetermined. Twenty-eight CHF patients underwent a symptom-limited incremental cardiopulmonary exercise test on a bicycle ergometer using a standardized exercise protocol of revised Ramp10 programs at Shanghai Tongji Hospital. Blood samples were collected before and immediately after an acute exercise session. RNA was extracted from the serum and selected miRNAs were determined using quantitative polymerase chain reactions. Moreover, inflammatory and muscle damage markers were determined by enzyme linked immunosorbent assays. We found that serum miR-21, miR-378 and miR-940 levels were significantly up-regulated immediately following an acute exercise while the rest were not changed. In addition, no robust correlation was identified between changes of these miRNAs and exercise capacity, muscle damage or inflammation. In conclusion, serum miR-21, miR-378, and miR-940 increase in response to an acute exhaustive exercise in CHF patients. Further studies are needed to clarify the potential use of circulating miRNAs as biomarkers of exercise adaptation in CHF patients, and if they have any use as prognostic markers of cardiovascular outcomes.
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http://dx.doi.org/10.18632/oncotarget.6966DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4914295PMC
March 2016

miR-212 downregulation contributes to the protective effect of exercise against non-alcoholic fatty liver via targeting FGF-21.

J Cell Mol Med 2016 Feb 9;20(2):204-16. Epub 2015 Dec 9.

Division of Gastroenterology and Hepatology, Digestive Disease Institute, Tongji Hospital, Tongji University School of Medicine, Shanghai, China.

Non-alcoholic fatty liver disease (NAFLD) is associated with obesity and lifestyle, while exercise is beneficial for NAFLD. Dysregulated microRNAs (miRs) control the pathogenesis of NAFLD. However, whether exercise could prevent NAFLD via targeting microRNA is unknown. In this study, normal or high-fat diet (HF) mice were either subjected to a 16-week running program or kept sedentary. Exercise attenuated liver steatosis in HF mice. MicroRNA array and qRT-PCR demonstrated that miR-212 was overexpressed in HF liver, while reduced by exercise. Next, we investigated the role of miR-212 in lipogenesis using HepG2 cells with/without long-chain fatty acid treatment (± FFA). FFA increased miR-212 in HepG2 cells. Moreover, miR-212 promoted lipogenesis in HepG2 cells (± FFA). Fibroblast growth factor (FGF)-21, a key regulator for lipid metabolism, was negatively regulated by miR-212 at protein level in HepG2 cells. Meanwhile, FFA downregulated FGF-21 both at mRNA and protein levels in HepG2 cells. Also, FGF-21 protein level was reduced in HF liver, while reversed by exercise in vivo. Furthermore, siRNA-FGF-21 abolished the lipogenesis-reducing effect of miR-212 inhibitor in HepG2 cells (± FFA), validating FGF-21 as a target gene of miR-212. These data link the benefit of exercise and miR-212 downregulation in preventing NAFLD via targeting FGF-21.
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http://dx.doi.org/10.1111/jcmm.12733DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4727558PMC
February 2016

Exercise as a platform for pharmacotherapy development in cardiac diseases.

Curr Pharm Des 2015 ;21(30):4409-16

Regeneration and Ageing Lab, Experimental Center of Life Sciences and Innovative Drug Research Center, School of Life Science, Shanghai University, 333 Nan Chen Road, Shanghai 200444, China.

Moderate exercise is an effective and economic way to prevent and treat cardiovascular diseases. Unlike pathological cardiac growth, exercise-induced cardiac growth, excluding extreme strenuous exercise, does not cause cardiac cell death, fibrosis, and cardiac dysfunction. The balanced cardiomyogenesis (cardiomyocyte hypertrophy and hyperplasia) and neo-angiogenesis are essential determinants for exercise-induced cardiac growth. In particular, exercise leads to physiological cardiac growth through regulating the IGF-1-PI3K-Akt, nitric oxide (NO), C/EBPβ, and PGC-1α signaling pathways, which might be novel therapeutic targets for cardiac diseases. The formation of new cardiomyocytes in response to exercise suggests that exercise might be a useful tool to enhance cardiac regenerative capacity. Exercise also exerts its protective effects against cardiac aging and cardiac metabolic derangement. Moreover, growing evidence reveals the regulation of cardiac and circulating microRNAs in response to exercise. A better understanding of the mechanisms underlying exercise-induced cardioprotection will lead to the development of innovative pharmacotherapies for cardiac diseases.
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http://dx.doi.org/10.2174/1381612821666150803150008DOI Listing
July 2016

Cardiac telocytes are double positive for CD34/PDGFR-α.

J Cell Mol Med 2015 Aug 17;19(8):2036-42. Epub 2015 Jun 17.

Regeneration and Ageing Lab, Experimental Center of Life Sciences, School of Life Science, Shanghai University, Shanghai, China.

Telocytes (TCs) are a distinct type of interstitial cells, which are featured with a small cellular body and long and thin elongations called telopodes (Tps). TCs have been widely identified in lots of tissues and organs including heart. Double staining for CD34/PDGFR-β (Platelet-derived growth factor receptor β) or CD34/Vimentin is considered to be critical for TC phenotyping. It has recently been proposed that CD34/PDGFR-α (Platelet-derived growth factor receptor α) is actually a specific marker for TCs including cardiac TCs although the direct evidence is still lacking. Here, we showed that cardiac TCs were double positive for CD34/PDGFR-α in primary culture. CD34/PDGFR-α positive cells (putative cardiac TCs) also existed in mice ventricle and human cardiac valves including mitral valve, tricuspid valve and aortic valve. Over 87% of cells in a TC-enriched culture of rat cardiac interstitial cells were positive for PDGFR-α, while CD34/PDGFR-α double positive cells accounted for 30.25% of the whole cell population. We show that cardiac TCs are double positive for CD34/PDGFR-α. Better understanding of the immunocytochemical phenotypes of cardiac TCs might help using cardiac TCs as a novel source in cardiac repair.
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http://dx.doi.org/10.1111/jcmm.12615DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4549054PMC
August 2015

Targeting microRNAs in Pathological Hypertrophy and Cardiac Failure.

Mini Rev Med Chem 2015 ;15(6):475-8

Regeneration and Ageing Lab, Experimental Center of Life Sciences and Innovative Drug Research Center, School of Life Science, Shanghai University, 333 Nan Chen Road, Shanghai 200444, China.

MicroRNAs (miRNAs) are a novel class of endogenous, short, non-coding, posttranscriptional RNAs, which play important roles in regulating lots of important biological functions. Evidences show that altered expression of miRNAs are involved in pathological hypertrophy and cardiac failure, making it possible to target miRNAs as a novel therapy. In this review, we focus on very recent progresses in the regulation of miRNAs in pathological hypertrophy and cardiac failure. In addition, we also discuss the potential of using miRNAs as a new therapy for pathological hypertrophy and cardiac failure.
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http://dx.doi.org/10.2174/1389557515666150324124751DOI Listing
July 2015
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