Publications by authors named "Chen-Yun Chen"

16 Publications

  • Page 1 of 1

Endothelial Reprogramming Stimulated by Oncostatin M Promotes Inflammation and Tumorigenesis in -Deficient Kidney Tissue.

Cancer Res 2021 Oct 23;81(19):5060-5073. Epub 2021 Jul 23.

Department of Biomedical Sciences and Engineering, National Central University, Taoyuan City, Taiwan, Republic of China.

Clear-cell renal cell carcinoma (ccRCC) is the most prevalent subtype of renal cell carcinoma (RCC), and its progression has been linked to chronic inflammation. About 70% of the ccRCC cases are associated with inactivation of the von Hippel-Lindau () tumor-suppressor gene. However, it is still not clear how mutations in , encoding the substrate-recognition subunit of an E3 ubiquitin ligase that targets the alpha subunit of hypoxia-inducible factor-α (HIFα), can coordinate tissue inflammation and tumorigenesis. We previously generated mice with conditional knockout in kidney tubules, which resulted in severe inflammation and fibrosis in addition to hyperplasia and the appearance of transformed clear cells. Interestingly, the endothelial cells (EC), although not subject to genetic manipulation, nonetheless showed profound changes in gene expression that suggest a role in promoting inflammation and tumorigenesis. Oncostatin M (OSM) mediated the interaction between -deficient renal tubule cells and the ECs, and the activated ECs in turn induced macrophage recruitment and polarization. The OSM-dependent microenvironment also promoted metastasis of exogenous tumors. Thus, OSM signaling initiates reconstitution of an inflammatory and tumorigenic microenvironment by -deficient renal tubule cells, which plays a critical role in ccRCC initiation and progression. SIGNIFICANCE: A novel mechanism of cross-talk between ECs and -deficient kidney tubules that stimulates inflammation and tumorigenesis is discovered, suggesting OSM could be a potential target for ccRCC intervention.
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http://dx.doi.org/10.1158/0008-5472.CAN-21-0345DOI Listing
October 2021

Cardiac-specific microRNA-125b deficiency induces perinatal death and cardiac hypertrophy.

Sci Rep 2021 01 27;11(1):2377. Epub 2021 Jan 27.

Cardiovascular Division, Institute of Biomedical Science, Academia Sinica, National Taiwan University College of Medicine, 128 Academia Road, Sec. 2, Nankang, Taipei, 115, Taiwan.

MicroRNA-125b, the first microRNA to be identified, is known to promote cardiomyocyte maturation from embryonic stem cells; however, its physiological role remains unclear. To investigate the role of miR-125b in cardiovascular biology, cardiac-specific miR-125b-1 knockout mice were generated. We found that cardiac-specific miR-125b-1 knockout mice displayed half the miR-125b expression of control mice resulting in a 60% perinatal death rate. However, the surviving mice developed hearts with cardiac hypertrophy. The cardiomyocytes in both neonatal and adult mice displayed abnormal mitochondrial morphology. In the deficient neonatal hearts, there was an increase in mitochondrial DNA, but total ATP production was reduced. In addition, both the respiratory complex proteins in mitochondria and mitochondrial transcription machinery were impaired. Mechanistically, using transcriptome and proteome analysis, we found that many proteins involved in fatty acid metabolism were significantly downregulated in miR-125b knockout mice which resulted in reduced fatty acid metabolism. Importantly, many of these proteins are expressed in the mitochondria. We conclude that miR-125b deficiency causes a high mortality rate in neonates and cardiac hypertrophy in adult mice. The dysregulation of fatty acid metabolism may be responsible for the cardiac defect in the miR-125b deficient mice.
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http://dx.doi.org/10.1038/s41598-021-81700-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7840921PMC
January 2021

Hypoxia-induced H19/YB-1 cascade modulates cardiac remodeling after infarction.

Theranostics 2019 21;9(22):6550-6567. Epub 2019 Aug 21.

Taiwan International Graduate Program in Molecular Medicine, National Yang-Ming University and Academia Sinica, Taipei, Taiwan.

Long non-coding RNA (lncRNAs) has been identified as a pivotal novel regulators in cardiac development as well as cardiac pathogenesis. lncRNA H19 is known as a fetal gene but it is exclusively abundant in the heart and skeletal muscles in adulthood, and is evolutionarily conserved in humans and mice. It has been reported to possess a significant correlation with the risk of coronary artery diseases. However, the function of H19 is not well characterized in heart. Loss-of-function and gain-of-function mouse models with left anterior descending coronary artery-ligation surgery were utilized to evaluate the functionality of H19 . For mechanistic studies, hypoxia condition were exerted in models to mimic cardiac ischemic injury. Chromatin isolation by RNA immunoprecipitation (ChIRP) was performed to reveal the interacting protein of lncRNA H19. lncRNA H19 was significantly upregulated in the infarct area post-surgery day 4 in mouse model. Ectopic expression of H19 in the mouse heart resulted in severe cardiac dilation and fibrosis. Several extracellular matrix (ECM) genes were significantly upregulated. While genetic ablation of H19 by CRISPR-Cas9 ameliorated post-MI cardiac remodeling with reduced expression in ECM genes. Through chromatin isolation by RNA purification (ChIRP), we identified Y-box-binding protein (YB)-1, a suppressor of Collagen 1A1, as an interacting protein of H19. Furthermore, H19 acted to antagonize YB-1 through direct interaction under hypoxia, which resulted in de-repression of Collagen 1A1 expression and cardiac fibrosis. Together these results demonstrate that lncRNA H19 and its interacting protein YB-1 are crucial for ECM regulation during cardiac remodeling.
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http://dx.doi.org/10.7150/thno.35218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6771230PMC
October 2020

MicroRNA let-7-TGFBR3 signalling regulates cardiomyocyte apoptosis after infarction.

EBioMedicine 2019 Aug 7;46:236-247. Epub 2019 Aug 7.

Institute of Biomedical Science, Academia Sinica, Taipei, Taiwan; Department of Medicine, University of Wisconsin-Madison, Madison, WI, United States; Department of Cell and Regenerative Biology, University of Wisconsin-Madison, Madison, WI, United States; Institute of Medical Genomics and Proteomics, National Taiwan University College of Medicine, Taipei, Taiwan; Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan; Division of Cardiovascular Surgery, Department of Surgery, National Taiwan University Hospital, Taipei 100, Taiwan. Electronic address:

Background: Myocardial infarction (MI) is a life-threatening disease, often leading to heart failure. Defining therapeutic targets at an early time point is important to prevent heart failure.

Methods: MicroRNA screening was performed at early time points after MI using paired samples isolated from the infarcted and remote myocardium of pigs. We also examined the microRNA expression in plasma of MI patients and pigs. For mechanistic studies, AAV9-mediated microRNA knockdown and overexpression were administrated in mice undergoing MI.

Findings: MicroRNAs let-7a and let-7f were significantly downregulated in the infarct area within 24 h post-MI in pigs. We also observed a reduction of let-7a and let-7f in plasma of MI patients and pigs. Inhibition of let-7 exacerbated cardiomyocyte apoptosis, induced a cardiac hypertrophic phenotype, and resulted in worsened left ventricular ejection fraction. In contrast, ectopic let-7 overexpression significantly reduced those phenotypes and improved heart function. We then identified TGFBR3 as a target of let-7, and found that induction of Tgfbr3 in cardiomyocytes caused apoptosis, likely through p38 MAPK activation. Finally, we showed that the plasma TGFBR3 level was elevated after MI in plasma of MI patients and pigs.

Interpretation: Together, we conclude that the let-7-Tgfbr3-p38 MAPK signalling plays an important role in cardiomyocyte apoptosis after MI. Furthermore, microRNA let-7 and Tgfbr3 may serve as therapeutic targets and biomarkers for myocardial damage. FUND: Ministry of Science and Technology, National Health Research Institutes, Academia Sinica Program for Translational Innovation of Biopharmaceutical Development-Technology Supporting Platform Axis, Thematic Research Program and the Summit Research Program, Taiwan.
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http://dx.doi.org/10.1016/j.ebiom.2019.08.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6712055PMC
August 2019

Primary cardiac manifestation of autosomal dominant polycystic kidney disease revealed by patient induced pluripotent stem cell-derived cardiomyocytes.

EBioMedicine 2019 Feb 11;40:675-684. Epub 2019 Jan 11.

Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan; Cellular and Molecular Arrhythmia Research Program, University of Wisconsin-Madison, Madison, WI, United States; Department of Medicine, University of Wisconsin-Madison, Madison, WI, United States. Electronic address:

Background: Mutations in PKD1 or PKD2 gene lead to autosomal dominant polycystic kidney disease (ADPKD). The mechanism of ADPKD progression and its link to increased cardiovascular mortality is still elusive.

Methods: We differentiated ADPKD patient induced pluripotent stem cells (iPSCs) to cardiomyocytes (CMs). The electrophysiological properties at the cellular level were analyzed by calcium imaging and whole cell patch clamping.

Findings: The ADPKD patient iPSC-CMs had decreased sarcoplasmic reticulum calcium content compared with Control-CMs. Spontaneous action potential of the PKD2 mutation line-derived CMs demonstrated slower beating rate and longer action potential duration. The PKD1 mutation line-derived CMs showed a comparable dose-dependent shortening of phase II repolarization with the Control-CMs, but a significant increase in beating frequency in response to L-type calcium channel blocker. The PKD1-mutant iPSC-CMs also showed a relatively unstable baseline as a greater percentage of cells exhibited delayed afterdepolarizations (DADs). Both the ADPKD patient iPSC-CMs showed more β-adrenergic agonist-elicited DADs compared with Control-CMs.

Interpretation: Characterization of ADPKD patient iPSC-CMs provides new insights into the increased clinical risk of arrhythmias, and the results enable disease modeling and drug screening for cardiac manifestations of ADPKD. FUND: Ministry of Science and Technology, National Health Research Institutes, Academia Sinica Program for Technology Supporting Platform Axis Scheme, Thematic Research Program and Summit Research Program, and Kaohsiung Medical University Hospital, Taiwan.
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http://dx.doi.org/10.1016/j.ebiom.2019.01.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6413318PMC
February 2019

Loss of Gut Microbiota Alters Immune System Composition and Cripples Postinfarction Cardiac Repair.

Circulation 2019 01;139(5):647-659

Program in Molecular Medicine, National Yang Ming University and Academia Sinica, Taipei, Taiwan (T.W.H.T., P.C.C.H.).

Background: The impact of gut microbiota on the regulation of host physiology has recently garnered considerable attention, particularly in key areas such as the immune system and metabolism. These areas are also crucial for the pathophysiology of and repair after myocardial infarction (MI). However, the role of the gut microbiota in the context of MI remains to be fully elucidated.

Methods: To investigate the effects of gut microbiota on cardiac repair after MI, C57BL/6J mice were treated with antibiotics 7 days before MI to deplete mouse gut microbiota. Flow cytometry was applied to examine the changes in immune cell composition in the heart. 16S rDNA sequencing was conducted as a readout for changes in gut microbial composition. Short-chain fatty acid (SCFA) species altered after antibiotic treatment were identified by high-performance liquid chromatography. Fecal reconstitution, transplantation of monocytes, or dietary SCFA or Lactobacillus probiotic supplementation was conducted to evaluate the cardioprotective effects of microbiota on the mice after MI.

Results: Antibiotic-treated mice displayed drastic, dose-dependent mortality after MI. We observed an association between the gut microbiota depletion and significant reductions in the proportion of myeloid cells and SCFAs, more specifically acetate, butyrate, and propionate. Infiltration of CX3CR1+ monocytes to the peri-infarct zone after MI was also reduced, suggesting impairment of repair after MI. Accordingly, the physiological status and survival of mice were significantly improved after fecal reconstitution, transplantation of monocytes, or dietary SCFA supplementation. MI was associated with a reorganization of the gut microbial community such as a reduction in Lactobacillus. Supplementing antibiotic-treated mice with a Lactobacillus probiotic before MI restored myeloid cell proportions, yielded cardioprotective effects, and shifted the balance of SCFAs toward propionate.

Conclusions: Gut microbiota-derived SCFAs play an important role in maintaining host immune composition and repair capacity after MI. This suggests that manipulation of these elements may provide opportunities to modulate pathological outcome after MI and indeed human health and disease as a whole.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.118.035235DOI Listing
January 2019

Characterization and functional correlation of multiple imaging modalities with focal choroidal excavation.

J Chin Med Assoc 2018 May 7;81(5):487-495. Epub 2018 Feb 7.

Department of Ophthalmology, Cheng Hsin General Hospital, Taipei, Taiwan, ROC.

Background: To investigate the clinical manifestations and imaging features of near-infrared autofluorescence (NIA), infrared reflectance (IR), fundus autofluorescence (FAF), indocyanine green angiography (ICGA) and fluorescein angiography (FAG) in the detection of patients with focal choroidal excavation (FCE) identified by cross-sectional spectral-domain optical coherence tomography (SD-OCT).

Methods: This retrospective cross-sectional study included 12 eyes of 10 Taiwanese patients with FCE diagnosed by SD-OCT. The areas and depths of FCE in serial cross-sectional and en-face OCT were compared in different imaging modalities. NIA, IR, FAF, ICGA and FAG images were obtained. Best corrected visual acuity, subjective distortion area in the Amsler grid and history of maculopathies were also recorded.

Results: In areas where the choroid started to excavate as shown in SD-OCT, hypo-autofluorescence in NIA was noted. The area of hypo-fluorescence in NIA of all the FCE lesions showed good correlation with the size. The area of FCE was associated with complications such as choroidal neovascularization and central serous chorioretinopathy (p = 0.014, d.f = 1) and the volume (NIA area × Depth measured by SD-OCT × 1/3) was associated with subjective distortion strongly (p = 0.051, Spearman's correlation = 0.600).

Conclusion: Among all image modalities, NIA was the most sensitive tool in area measurement of FCE and peripheral lesion detection. Also, the volume of FCE was associated with subjective distortion and the area was related to complications. Recording the area and volume of FCE could play an important role in monitoring complications.
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http://dx.doi.org/10.1016/j.jcma.2017.07.017DOI Listing
May 2018

Rapid resolution of stromal keratitis with the assistance of oral voriconazole in resistant acanthamoeba keratitis.

Taiwan J Ophthalmol 2017 Oct-Dec;7(4):224-226

Department of Ophthalmology, Taipei Veterans General Hospital, Taipei, Taiwan.

Acanthamoeba keratitis (AK) is an unusual infectious disease of the cornea which sometimes leads to blindness. We report the experience of adding oral voriconazole in conjunction with topical antiacanthamoebic drops to treat refractory AK. A 20-year-old girl experienced a deep stromal keratitis with large epithelial defect in the left eye, suspected as AK. The initial best-corrected visual acuity (BCVA) of the eye was counting finger. She received topical chlorhexidine 0.02% and voriconazole 1% during the first 14 days but in vain. Oral voriconazole was administered and resulted in a rapid regression of the lesion. A total resolution was achieved after 2 weeks of triple combination therapy. The BCVA of the left eye finally achieved 20/20 at 6-month follow-up. Although oral voriconazole was seldom used in treating acute AK, the additional use of oral voriconazole combined with topical antiacanthamoebic drugs may help to achieve a successful treatment effect in refractory stromal AK.
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http://dx.doi.org/10.4103/tjo.tjo_73_17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5747234PMC
January 2018

The roles of non-coding RNAs in cardiac regenerative medicine.

Noncoding RNA Res 2017 Jun 7;2(2):100-110. Epub 2017 Jun 7.

Taiwan International Graduate Program in Molecular Medicine, National Yang-Ming University and Academia Sinica, Taipei, Taiwan.

The emergence of non-coding RNAs (ncRNAs) has challenged the central dogma of molecular biology that dictates that the decryption of genetic information starts from transcription of DNA to RNA, with subsequent translation into a protein. Large numbers of ncRNAs with biological significance have now been identified, suggesting that ncRNAs are important in their own right and their roles extend far beyond what was originally envisaged. ncRNAs do not only regulate gene expression, but are also involved in chromatin architecture and structural conformation. Several studies have pointed out that ncRNAs participate in heart disease; however, the functions of ncRNAs still remain unclear. ncRNAs are involved in cellular fate, differentiation, proliferation and tissue regeneration, hinting at their potential therapeutic applications. Here, we review the current understanding of both the biological functions and molecular mechanisms of ncRNAs in heart disease and describe some of the ncRNAs that have potential heart regeneration effects.
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http://dx.doi.org/10.1016/j.ncrna.2017.06.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6096405PMC
June 2017

Mechanisms of pluripotency maintenance in mouse embryonic stem cells.

Cell Mol Life Sci 2017 05 20;74(10):1805-1817. Epub 2016 Dec 20.

Institute of Biomedical Sciences, Academia Sinica, IBMS Rm.417, 128 Academia Road, Section 2, Nankang, Taipei, 115, Taiwan.

Mouse embryonic stem cells (mESCs), characterized by their pluripotency and capacity for self-renewal, are driven by a complex gene expression program composed of several regulatory mechanisms. These mechanisms collaborate to maintain the delicate balance of pluripotency gene expression and their disruption leads to loss of pluripotency. In this review, we provide an extensive overview of the key pillars of mESC pluripotency by elaborating on the various essential transcription factor networks and signaling pathways that directly or indirectly support this state. Furthermore, we consider the latest developments in the role of epigenetic regulation, such as noncoding RNA signaling or histone modifications.
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http://dx.doi.org/10.1007/s00018-016-2438-0DOI Listing
May 2017

Bcl3 Bridges LIF-STAT3 to Oct4 Signaling in the Maintenance of Naïve Pluripotency.

Stem Cells 2015 Dec 18;33(12):3468-80. Epub 2015 Sep 18.

Program in Molecular Medicine, National Yang-Ming University and Academia Sinica, Taipei, Taiwan.

Leukemia inhibitory factor (LIF) regulates mouse embryonic stem cell (mESC) pluripotency through STAT3 activation, but the downstream signaling remains largely unelucidated. Using cDNA microarrays, we verified B cell leukemia/lymphoma 3 (Bcl3) as the most significantly downregulated factor following LIF withdrawal in mESCs. Bcl3 knockdown altered mESC morphology, reduced expression of pluripotency genes including Oct4, Sox2, and Nanog, and downregulated DNA binding of acetylated histone 3 and RNA polymerase II on the Oct4 promoter. Conversely, Bcl3 overexpression partially prevented cell differentiation and promoted Oct4 and Nanog promoter activities. Furthermore, coimmunoprecipitation and chromatin immunoprecipitation experiments demonstrated that Bcl3 regulation of mESC pluripotency may be through its association with Oct4 and β-catenin and its promoter binding capability. These results establish that Bcl3 positively regulates pluripotency genes and thus shed light on the mechanism of Bcl3 as a downstream molecule of LIF/STAT3 signaling in pluripotency maintenance.
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http://dx.doi.org/10.1002/stem.2201DOI Listing
December 2015

Modeling pegylated liposomal doxorubicin-induced hand-foot syndrome and intestinal mucositis in zebrafish.

Onco Targets Ther 2014 1;7:1169-75. Epub 2014 Jul 1.

Graduate Institute of Pharmacology, Taipei Medical University, Taipei, Taiwan ; Department of Radiation Oncology, Mackay Memorial Hospital, Taipei, Taiwan.

Pegylated liposomal doxorubicin (PLD) has been widely used to treat cancer. The adverse effects of PLD noted in clinical practice, especially hand-foot syndrome (HFS), are regarded as unique, and the management methods for them remain limited. This study was aimed at developing a feasible experimental model for translational medicine to solve this clinical issue by using skin fluorescent transgenic zebrafish. We established an optimal protocol for the administration of Lipo-Dox™, a PLD in current clinical use, to the Tg(k18:dsred) zebrafish line expressing red fluorescence in keratinocytes. We made use of bodyweight, survival rate, gross observation, flssuorescent microscopic assessment, and pathological examination of the zebrafish to assess this model. The consecutive administration protocol of PLD resulted in growth retardation of the zebrafish embryo and survival impairment, indicating establishment of a significant toxicity. We observed fin necrosis and keratinocyte dissociation phenotypes in the PLD-treated fish after consecutive administration. The skin toxicity induced by the Lipo-Dox injection was subsequently reversible, which might be compatible with a clinical course of skin recovery after discontinuation of Lipo-Dox administration. Furthermore, we found that the number of intestinal goblet cells, an important marker of intestinal inflammation, in the Lipo-Dox-injected zebrafish was markedly increased, accompanied by impaired mucosal integrity. The intestinal inflammation induced by Lipo-Dox resembled the intestinal mucositis the clinical patients suffered from after the administration of PLD. In conclusion, we established a zebrafish model for PLD-induced HFS. The intestinal mucositis simultaneously noted in the PLD-treated zebrafish validated the similarity of clinical courses after administration of PLD. This model is easily assessable, efficient, and worthy for use in developing a new therapeutic protocol for prevention or treatment of HFS as well as intestinal mucositis. Further clinical investigations to validate the correlation between human and zebrafish data are warranted.
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http://dx.doi.org/10.2147/OTT.S63785DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4085292PMC
July 2014

Embryonic exposure to diclofenac disturbs actin organization and leads to myofibril misalignment.

Birth Defects Res B Dev Reprod Toxicol 2011 Apr 17;92(2):139-47. Epub 2011 Mar 17.

Institute of Medical Sciences, Buddhist Tzu Chi University, Hualien, Taiwan.

The objective of this study was to investigate the embryotoxicity of diclofenac. Zebrafish (Danio rerio) embryos at 12 hpf were treated with different dosages of diclofenac (0-2,000 ppm) for different time courses (12-72 hr). Results showed no evident differences in survival rates or morphological changes between the mock-treated control (0 ppm) zebrafish embryos and those with 1-ppm diclofenac-exposure (12-24, 12-36 hpf). In contrast, after higher doses (5 and 10 ppm) of exposure, embryos displayed some defective phenotypes, including malformed somite boundary, a twisted body axis, and shorter body length. In addition, diclofenac-treated embryos exhibited significantly reduced frequencies of spontaneous in-chorion contractions in comparison with mock-control littermates (mock-control: 13.20 ± 2.24 vs. 5-10 ppm diclofenac: 6.66 ± 1.35-3.03 ± 1.84). Subtle changes were easily observed by staining with specific monoclonal antibodies F59 and phalloidin to detect morphological changes in muscle fibers and formation of F-actin, respectively. Our data show that diclofenac treatment disturbs actin organization and muscle fiber alignment, thus causing malformed somite phenotypes.
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http://dx.doi.org/10.1002/bdrb.20292DOI Listing
April 2011

Fibroblast growth factor-10 promotes cardiomyocyte differentiation from embryonic and induced pluripotent stem cells.

PLoS One 2010 Dec 28;5(12):e14414. Epub 2010 Dec 28.

Institute of Clinical Medicine and Research Center for Clinical Medicine, National Cheng Kung University and Hospital, Tainan, Taiwan.

Background: The fibroblast growth factor (FGF) family is essential to normal heart development. Yet, its contribution to cardiomyocyte differentiation from stem cells has not been systemically studied. In this study, we examined the mechanisms and characters of cardiomyocyte differentiation from FGF family protein treated embryonic stem (ES) cells and induced pluripotent stem (iPS) cells.

Methodology/principal Findings: We used mouse ES cells stably transfected with a cardiac-specific α-myosin heavy chain (αMHC) promoter-driven enhanced green fluorescent protein (EGFP) and mouse iPS cells to investigate cardiomyocyte differentiation. During cardiomyocyte differentiation from mouse ES cells, FGF-3, -8, -10, -11, -13 and -15 showed an expression pattern similar to the mesodermal marker Brachyury and the cardiovascular progenitor marker Flk-1. Among them, FGF-10 induced cardiomyocyte differentiation in a time- and concentration-dependent manner. FGF-10 neutralizing antibody, small molecule FGF receptor antagonist PD173074 and FGF-10 and FGF receptor-2 short hairpin RNAs inhibited cardiomyocyte differentiation. FGF-10 also increased mouse iPS cell differentiation into cardiomyocyte lineage, and this effect was abolished by FGF-10 neutralizing antibody or PD173074. Following Gene Ontology analysis, microarray data indicated that genes involved in cardiac development were upregulated after FGF-10 treatment. In vivo, intramyocardial co-administration of FGF-10 and ES cells demonstrated that FGF-10 also promoted cardiomyocyte differentiation.

Conclusion/significance: FGF-10 induced cardiomyocyte differentiation from ES cells and iPS cells, which may have potential for translation into clinical applications.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0014414PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3011000PMC
December 2010

A novel function of transcription factor alpha-Pal/NRF-1: increasing neurite outgrowth.

Biochem Biophys Res Commun 2005 Aug;334(1):199-206

Institute of Basic Medical Sciences, National Cheng Kung University College of Medicine, Tainan 701, Taiwan.

Alpha-Pal/NRF-1 is a critical regulator of the promoter of human IAP/CD47 gene, a gene related to memory formation in rodents. However, its function in neurons was unknown. We found that stable or transient expression of full-length alpha-Pal/NRF-1 in human neuroblastoma IMR-32 cells significantly induced neurite outgrowth and increased the length of neurites both in medium containing 10% fetal bovine serum and in serum-free medium. In contrast, the dominant-negative mutant of alpha-Pal/NRF-1 inhibited the induction and extension of neurites. Ectopic expression of full-length alpha-Pal/NRF-1 also increased the induction of neurite outgrowth in primary mouse cortical neurons. The IAP antisense cDNA significantly inhibited the increase of neurite outgrowth by alpha-Pal/NRF-1. These findings indicate that a novel function of alpha-Pal/NRF-1 is to regulate neuronal differentiation, and that this function is mediated partly via its downstream IAP gene.
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http://dx.doi.org/10.1016/j.bbrc.2005.06.079DOI Listing
August 2005

Inhibitory effect of red koji extracts on mushroom tyrosinase.

J Agric Food Chem 2003 Jul;51(15):4240-6

Department of Applied Chemistry, National Chi-Nan University, Puli, Nantou 545, Taiwan.

Red koji has been recognized as a cholesterol-lowering diet supplement because of it contains fungi metabolites, monacolins, which reduce cholesterol synthesis by inhibiting HMG-CoA reductase. In this study, water extracts of red koji were loaded onto a C(18) cartridge, and the acetonitrile eluate was collected as test fraction. Red koji water extracts and its C(18) cartridge acetonitrile eluent had total phenols concentrations of 5.57 and 1.89 mg/g of red koji and condensed tannins concentrations of 2.71 and 1.20 mg/g of red koji, respectively. Both exhibited an antioxidant activity and an inhibitory activity to mushroom tyrosinase. The higher antioxidant activity of the red koji acetonitrile eluent was due to the existence of a high percentage of condensed tannins. The results from the kinetic study for inhibition of mushroom tyrosinase by red koji extracts showed that the compounds in the extracts competitively inhibited the oxidation of tyrosine catalyzed by mushroom tyrosinase with an ID(50) of 5.57 mg/mL.
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http://dx.doi.org/10.1021/jf034064fDOI Listing
July 2003
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