Search Our Scientific Publications & Authors

EBioMedicine 2019 Feb 13. Epub 2019 Feb 13.

Department of Internal Medicine, Michigan Medicine, Ann Arbor, MI, USA. Electronic address:

Background: Nonalcoholic fatty liver disease (NAFLD) and resulting nonalcoholic steatohepatitis (NASH) are reaching global epidemic proportions. Lack of non-invasive diagnostic tools and effective therapies constitute two of the major hurdles for a bona fide treatment and a reversal of NASH progression and/or regression of the disease. Nitro-oleic acid (OA-NO) has been proven effective in multiple experimental models of inflammation and fibrosis. Read More

J Cell Biochem 2019 Feb 14. Epub 2019 Feb 14.

Department of Respiratory Medicine, Shenzhen Luohu People's Hospital, The Third Affiliated Hospital of Shenzhen University, Guangdong, Shenzhen, China.

Pulmonary fibrosis is a lethal inflammatory disease. In this study, we aimed to explore the potential-related circular RNAs (circRNAs) and genes that are associated with pulmonary fibrosis. Pulmonary fibrosis rat models were constructed and the fibrosis deposition was detected using hematoxylin and eosin and Masson staining. Read More

Hepatol Commun 2019 Feb 13;3(2):180-192. Epub 2018 Dec 13.

Department of Surgery University of California San Diego La Jolla CA.

Hepatic fibrosis results from chronic injury and inflammation in the liver and leads to cirrhosis, liver failure, and portal hypertension. Understanding the molecular mechanisms underlying hepatic fibrosis has advanced the prospect of developing therapies for regression of the disease. Resolution of fibrosis requires a reduction of proinflammatory and fibrogenic cytokines, a decrease in extracellular matrix (ECM) protein production, an increase in collagenase activity, and finally, a disappearance of activated myofibroblasts. Read More

Br J Pharmacol 2019 Feb 12. Epub 2019 Feb 12.

Experimental Cardiology Laboratory, Baker Heart and Diabetes Institute, Melbourne, Australia.

Myocardial fibrosis is a key histopathological component that drives the progression of heart disease leading to heart failure and forms a therapeutic target. Recent preclinical and clinical studies have implicated galectin-3 (Gal-3) as a pro-fibrotic molecule and a biomarker of heart disease and fibrosis. However, our knowledge is poor on the mechanism(s) that determine the blood level or regulate cardiac expression of Gal-3. Read More

Cell Death Dis 2019 Feb 12;10(2):129. Epub 2019 Feb 12.

First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, 250355, People's Republic of China.

Long non-coding RNAs (lncRNAs) have been reported to be involved in various pathophysiological processes in many diseases. However, the role and mechanism of lncRNAs in pulmonary fibrosis have not been explicitly delineated. In the present study, we found that lncRNA ZEB1 antisense RNA 1 (ZEB1-AS1) is upregulated in the lungs of BLM-induced rats and TGF-β1-induced RLE-6TN cells, and positively correlated with the levels of ZEB1, an epithelial-mesenchymal transition (EMT) master regulator. Read More

Cardiovasc Res 2019 Feb 7. Epub 2019 Feb 7.

Research Center of the Montreal Heart Institute.

Aims: Heart failure with reduced ejection fraction (HFrEF) causes lung remodelling with myofibroblasts proliferation and fibrosis leading to a restrictive lung syndrome with pulmonary hypertension (PH) and right ventricular (RV) dysfunction. PBI-4050 is a first-in-class anti-fibrotic, anti-inflammatory and anti-proliferative compound. The present study evaluated the therapeutic impact of PBI-4050 on PH in an HFrEF model. Read More

FASEB J 2019 Feb 11:fj201801256RR. Epub 2019 Feb 11.

Department of Life Sciences, School of Life Sciences and Biotechnology, Korea University, Seoul, South Korea.

In response to liver injury, the liver undergoes a regeneration process to retain its mass and function. However, the regeneration mechanism has not been fully clarified. This study investigated the role of transcriptional coactivator with PDZ-binding motif (TAZ), a Hippo-signaling effector, in liver regeneration. Read More

Inflammation 2019 Feb 11. Epub 2019 Feb 11.

Department of Biology, College of Science, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia.

Umbelliferone (UMB) is a natural coumarin that has diverse biological activities. However, its potential to protect against liver fibrosis has not been reported yet. This study aimed to investigate the protective effect of UMB against carbon tetrachloride (CCl)-induced liver fibrosis in rats. Read More

J Exp Med 2019 Feb 7. Epub 2019 Feb 7.

Department of Molecular Medicine, University of Pavia, Pavia, Italy

The fibronectin EDA isoform (EDA FN) is instrumental in fibrogenesis but, to date, its expression and function in bone marrow (BM) fibrosis have not been explored. We found that mice constitutively expressing the EDA domain (EIIIA), but not EDA knockout mice, are more prone to develop BM fibrosis upon treatment with the thrombopoietin (TPO) mimetic romiplostim (TPO). Mechanistically, EDA FN binds to TLR4 and sustains progenitor cell proliferation and megakaryopoiesis in a TPO-independent fashion, inducing LPS-like responses, such as NF-κB activation and release of profibrotic IL-6. Read More

Ther Adv Ophthalmol 2019 Jan-Dec;11:2515841418817500. Epub 2019 Jan 18.

Queen Victoria Hospital NHS Foundation Trust, East Grinstead, UK.

Purpose: To present a case of a complicated intracorneal ring segment (ICRS) implantation procedure in a patient with keratoconus, who experienced significant visual improvement, although the ICRS implantation had to be aborted.

Methods: A 25-year-old female patient with keratoconus underwent femtosecond laser-assisted ICRS implantation in her right eye (OD) for improving visual acuity.

Results: The procedure had to be aborted, because ICRS implantation was not possible. Read More

Hepatology 2019 Feb 5. Epub 2019 Feb 5.

Children's Hospital Los Angeles, Surgery, Los Angeles, CA, USA.

Background: In patients with biliary atresia (BA), the extent of intrahepatic biliary fibrosis negatively correlates with successful surgical bypass of the congenital cholangiopathy as well as subsequent transplant-free survival. We recently linked the expansion of a population of Prominin-1 (Prom1)-expressing hepatic progenitor cells to biliary fibrogenesis. Herein, we hypothesized that Prom1-expressing progenitor cells play a role in BA-associated fibrosis. Read More

J Mol Med (Berl) 2019 Feb 5. Epub 2019 Feb 5.

Storr Liver Unit, Westmead Millennium Institute and Westmead Hospital, University of Sydney, Westmead, NSW, 2145, Australia.

Recent studies have indicated that the Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) pathway is closely involved in liver fibrosis and other fibrotic diseases. However, whether targeting the AMPK pathway can rescue liver fibrosis and its complications, such as portal hypertension, is unknown. This study aimed to explore the therapeutic value of AICAR (5-aminoimidazole-4-carboxyamide ribonucleoside), an agonist of the AMPK pathway, on liver fibrosis and portal hypertension in bile duct ligation (BDL) rats. Read More

Mol Med Rep 2019 Jan 24. Epub 2019 Jan 24.

Department of Cardiology, Zhejiang Hospital, Hangzhou, Zhejiang 310013, P.R. China.

Cardiac fibrosis is closely associated with various heart diseases and is an important pathological feature of cardiac remodeling. However, detailed mechanisms underlying cardiac fibrosis remain largely unknown. Long noncoding RNAs (lncRNAs) are reported to serve significant roles in the development of cardiac fibrosis. Read More

Cell Signal 2019 Jan 31. Epub 2019 Jan 31.

Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai, PR China; Shanghai Institute of Liver disease, Shanghai, PR China. Electronic address:

Epithelial-mesenchymal transition (EMT) has emerged as a vital process in embryogenesis, carcinogenesis, and tissue fibrosis. Transforming growth factor-beta 1 (TGF-β1)-mediated signaling pathways play important roles in the EMT process. MicroRNA-146a (miR-146a) has been suggested as a significant regulatory molecule in fibrogenesis. Read More

Chem Biol Interact 2019 Jan 28;302:53-60. Epub 2019 Jan 28.

Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt.

The current study was designed to assess the antifibrotic effect of dimethylfumarate (DMF) on CCl-induced hepatic injury in rats. Hepatic injury was induced by intraperitoneal twice weekly injection of CCl for 2 and 3 months. DMF was administered orally during the last 4 weeks in each model. Read More

Ter Arkh 2018 Feb;90(2):79-84

A.I. Evdokimov Moscow State University of Medicine and Dentistry, Ministry of Health of Russia, Moscow, Russia.

The review presents modern data on the cellular and molecular mechanisms of inflammatory changes of esophageal mucosa exposed to different types of reluctate (gastric, biliary or duodenal/mixed). The authors describe data on key mediators of inflammation in gastroesophageal reflux disease (GERD) and their major cellular sources, changes of the immune profile of patients. Discusses the possible impact of changes in the cellular and molecular components in the development of the inflammatory response in the esophagus on the clinical features of GERD and its therapy-refractory forms. Read More

Cancer Res 2019 Jan 29. Epub 2019 Jan 29.

Department of Cancer Biology, Mayo Clinic

During development of pancreatic cancer, alternatively-activated macrophages contribute to fibrogenesis, pancreatic intraepithelial neoplasia (PanIN) lesion growth, and generation of an immunosuppressive environment. Here we show that the immunomodulatory agent pomalidomide depletes pancreatic lesion areas of alternatively-activated macrophage populations. Pomalidomide treatment resulted in downregulation of interferon regulatory factor 4 (IRF4), a transcription factor for M2 macrophage polarization. Read More

PLoS Biol 2019 Jan 29;17(1):e2006972. Epub 2019 Jan 29.

CIBERDEM (Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas), Madrid, Spain.

Insulin provides important information to tissues about feeding behavior and energy status. Defective insulin signaling is associated with ageing, tissue dysfunction, and impaired wound healing. In the liver, insulin resistance leads to chronic damage and fibrosis, but it is unclear how tissue-repair mechanisms integrate insulin signals to coordinate an appropriate injury response or how they are affected by insulin resistance. Read More

Gastroenterology 2019 Jan 25. Epub 2019 Jan 25.

Institute for Regenerative Medicine; Penn Epigenetics Institute; Dept. Cell and Developmental Biology; Perelman School of Medicine, University of Pennsylvania, Smilow Center for Translational Research, 3400 Civic Center Blvd, Bldg. 421, Philadelphia, PA 19104-5157, USA. Electronic address:

Background & Aims: Little is known about mechanisms of postnatal hepatocyte maturation or chromatin regulation of genes that control fibrogenesis. We investigated transcription of genes that regulate fibrosis and the effects of chromatin compaction and the polycomb repressive complex 2 (PRC2) in postnatal hepatocytes of mice, focusing on the roles of the histone methyltransferases EZH1 and EZH2.

Methods: Hepatocytes were isolated from C57BL/6J and C3H mice, as well as mice with liver-specific disruption of Ezh1 and/or Ezh2, at postnatal day 14 (P14) and 2 months after birth (M2). Read More

Glycobiology 2019 Jan 25. Epub 2019 Jan 25.

University of Eastern Finland, Faculty of Health Sciences, School of Medicine, Institute of Biomedicine, Kuopio, Finland.

Non-alcoholic fatty liver disease is among the most common liver diseases worldwide and one cause of cirrhosis that can result in the development of hepatocellular carcinoma (HCC). Hyaluronan (HA) is a high-molecular-mass glycosaminoglycan with diverse functions in tissue injury and repair, for instance, in inflammation and fibrogenesis. The aim of the present study was to investigate the relationships between the HA synthesizing and degrading enzymes in a spectrum of liver pathologies. Read More

Hum Reprod 2019 Jan 28. Epub 2019 Jan 28.

Shanghai OB/GYN Hospital, Fudan University, Shanghai, China.

Study Question: Do sensory nerves play any role in the development of endometriosis?

Summary Answer: Sensory nerves participate in all major steps (epithelial-mesenchymal transition (EMT), fibroblast-to-myofibroblast transdifferentiation (FMT) and smooth muscle metaplasia (SMM)) in the development and fibrogenesis of endometriotic lesions.

What Is Known Already: Endometriotic lesions are known to be hyperinnervated due to neurogenesis resulting from neutrophins secreted by endometriotic lesions and possibly platelets. These neutrophins seem to preferentially favour production of sensory neurons at the expense of sympathetic neurons. Read More

Biomed Res Int 2018 30;2018:6137420. Epub 2018 Dec 30.

Department of Surgery, University of Texas Medical Branch, Galveston, Texas, 77555, USA.

Hepatic stellate cells (HSCs) play an important role in hepatic fibrogenesis and inflammatory modulation. Endotoxin is dramatically increased in portal venous blood after serious injury and can contribute to liver damage. However, the mechanism underlying endotoxin's effects on HSCs remains largely unknown. Read More

Surgery 2019 Jan 24. Epub 2019 Jan 24.

Pediatric Surgery and Pediatric Transplantation Surgery, Pediatric Liver and Gut Research Group, Children's Hospital, University of Helsinki and Helsinki University Hospital, Finland.

Background: Pathogenesis of progressive liver fibrosis in biliary atresia after successful portoenterostomy remains unclear. We related hepatic expression of transforming growth factor beta (TGF-β) superfamily cytokines to histologic liver injury after successful portoenterostomy.

Methods: Enrolled in our study were 28 patients with biliary atresia who had liver biopsies obtained during and after successful portoenterostomy, which normalized serum bilirubin (<20 µmol/l). Read More

Sci Rep 2019 Jan 24;9(1):716. Epub 2019 Jan 24.

National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, 210002, China.

Tubulointerstitial fibrosis impacts renal prognosis of focal segmental glomerulosclerosis (FSGS). Based on transcriptomic analysis, we found that the level of LOC105375913 was increased in tubular cells of FSGS patients. C3a induced the expression of LOC105375913, which promoted the expression of fibronectin and collagen I in tubular cells. Read More

Commun Biol 2019 16;2:20. Epub 2019 Jan 16.

Cardiometabolic Disorders Therapeutic Area, Amgen Research, South San Francisco, CA USA.

Cardiovascular disease is expected to remain the leading cause of death worldwide despite the introduction of proprotein convertase subtilisin/kexin type 9 inhibitors that effectively control cholesterol. Identifying residual risk factors for cardiovascular disease remains an important step for preventing and clinically managing the disease. Here we report cardiac injury and increased mortality occurring despite a 50% reduction in plasma cholesterol in a mouse model of phytosterolemia, a disease characterized by elevated levels of dietary plant sterols in the blood. Read More

Stem Cells Int 2018 24;2018:3212643. Epub 2018 Dec 24.

Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo 0608638, Japan.

Background: There are no approved drug treatments for liver fibrosis and nonalcoholic steatohepatitis (NASH), an advanced stage of fibrosis which has rapidly become a major cause of cirrhosis. Therefore, development of anti-inflammatory and antifibrotic therapies is desired. Mesenchymal stem cell- (MSC-) based therapy, which has been extensively investigated in regenerative medicine for various organs, can reportedly achieve therapeutic effect in NASH via paracrine action. Read More

Dig Dis Sci 2019 Jan 23. Epub 2019 Jan 23.

Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Wenzhou Medical University, 205 Wenrui Avenue, Wenzhou, 325000, People's Republic of China.

Background: The activation of hepatic stellate cells (HSCs) is involved in hepatic fibrogenesis and is regulated by the decreased expression of peroxisome proliferator-activated receptor γ (PPARγ). Rosiglitazone (RGZ) is a highly potent agonist of PPARγ.

Aims: To clarify molecular regulatory mechanism of RGZ in the activation of HSCs in hepatic fibrosis. Read More

Drug Des Devel Ther 2019 11;13:285-290. Epub 2019 Jan 11.

Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, P.R. China.

Aim: To testify the hypothesis that endostatin exerts antifibrotic effects in hepatic stellate cells (HSCs) by modulating RhoA (ras homolog gene family, member A)/ROCK 1 (Rho-associated protein kinase 1) signal pathways.

Materials And Methods: HSCs-T6 of passages 3-5 were cultured in DMEM and serum starved for 48 hours. HSCs were grouped as follows: control group, TGF-β1 (transforming growth factor β1) group, endostatin+TGF-β1 group, PDGF-BB (platelet-derived growth factor-BB) group, and endostatin+PDGF-BB group. Read More

Curr Pharm Des 2019 Jan 18. Epub 2019 Jan 18.

Internal Medicine and Metabolic Diseases, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico. Italy.

Nonalcoholic fatty liver disease (NAFLD), now the leading cause of liver damage worldwide, is epidemiologically associated with obesity, insulin resistance and type 2 diabetes, and is a potentially progressive condition to advanced liver fibrosis and hepatocellular carcinoma. However, there is a huge interindividual variability in liver disease susceptibility. Inherited factors play also an important role in determining disease predisposition. Read More

J Clin Med 2019 Jan 17;8(1). Epub 2019 Jan 17.

Department of Internal Medicine II, Saarland University Medical Center, 66421 Homburg, Germany.

Vascular adhesion protein-1 (VAP-1) is a multifunction protein. While membrane-bound VAP-1 is an adhesion protein, soluble VAP-1 catalyzes the deamination of primary amines through its semicarbazide-sensitive amino oxidase (SSAO) activity. VAP-1 supports the transmigration of leukocytes and increases oxidative stress. Read More

Oxid Med Cell Longev 2018 17;2018:5045734. Epub 2018 Dec 17.

Department of Biology and Evolution of Marine Organisms, Stazione Zoologica Anton Dohrn, Naples, Italy.

Liver fibrosis is a complex process caused by chronic hepatic injury, which leads to an excessive increase in extracellular matrix protein accumulation and fibrogenesis. Several natural products, including sulfur-containing compounds, have been investigated for their antifibrotic effects; however, the molecular mechanisms underpinning their action are partially still obscure. In this study, we have investigated for the first time the effect of ovothiol A, -methyl-5-thiohistidine, isolated from sea urchin eggs on an murine model of liver fibrosis. Read More

Biochem Cell Biol 2019 Jan 15. Epub 2019 Jan 15.

Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China ;

Aberrant expression of microRNAs is associated with liver fibrogenesis. We previously found that microRNA-134 (miR-134) expression was reduced in fibrosis-based hepatocarcinogenesis induced by diethylinitrosamine. Herein we investigate the role and mechanisms of miR-134 in hepatic fibrosis. Read More

Cell Death Differ 2019 Jan 15. Epub 2019 Jan 15.

Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang, 150081, People's Republic of China.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrotic parenchymal lung disease of unknown etiology and lack effective interventions. Using a combination of in vitro and in vivo studies, we found that overexpression of YAP1, a key effector in the Hippo pathway, promoted cell proliferation, migration, and collagen production in lung fibroblasts. Furthermore, the pro-fibrotic action of YAP1 was mediated by transcriptional activation of Twist1 through interacting with its partner TEAD. Read More

Biomed Res Int 2018 12;2018:4706976. Epub 2018 Dec 12.

Chemistry Department, Basic Sciences Center, Autonomous University of Aguascalientes, Mexico.

Regulation of the mechanisms of fibrosis is an important goal in the treatment of liver cirrhosis. One mechanism is the participation of hepatic stellate cells in fibrogenesis when activated by catecholamines. Consequently, / adrenoblockers are proposed as an alternative treatment for chronic liver lesions such as fibrosis and/or cirrhosis and for possible liver regeneration. Read More

Nat Immunol 2019 Feb 14;20(2):163-172. Epub 2019 Jan 14.

Division of Pulmonary, Critical Care, Allergy, and Sleep Medicine, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.

Tissue fibrosis is a major cause of mortality that results from the deposition of matrix proteins by an activated mesenchyme. Macrophages accumulate in fibrosis, but the role of specific subgroups in supporting fibrogenesis has not been investigated in vivo. Here, we used single-cell RNA sequencing (scRNA-seq) to characterize the heterogeneity of macrophages in bleomycin-induced lung fibrosis in mice. Read More

Z Gastroenterol 2019 Jan 14;57(1):37-45. Epub 2019 Jan 14.

Department of Medicine and Liver Diseases, Salem Medical Center, University of Heidelberg, Germany.

Various factors are involved in the pathogenesis of alcoholic liver disease (ALD) and ethanol-mediated carcinogenesis. In addition to genetic, epigenetic and immunologic mechanisms, acetaldehyde-associated toxicity, oxidative stress as well as cytokine-mediated inflammation are of major importance. Oxidative stress, with the generation of reactive oxygen species (ROS), develops either in inflammation (alcoholic hepatitis) or during oxidation of ethanol via cytochrome P4502E1 (CYP2E1). Read More

Cells Tissues Organs 2019 Jan 10:1-11. Epub 2019 Jan 10.

Reference and Translation Center for Cardiac Stem Cell Therapy (RTC), Rostock University Medical Center, Rostock, Germany.

In-depth knowledge of the mechanisms induced by early postischemic cardiac endogenous mesenchymal stem cells (MSCs) in the acutely ischemic heart could advance our understanding of cardiac regeneration. Herein, we aimed to identify, isolate, and initially characterize the origin, kinetics and fate of cardiac MSCs. This was facilitated by in vivo genetic cell fate mapping through green fluorescent protein (GFP) expression under the control of vimentin induction after acute myocardial infarction (MI). Read More

Cell Death Dis 2019 Jan 8;10(1):14. Epub 2019 Jan 8.

Department of Gene Therapy and Hepatology, Center for Applied Medical Research (CIMA), University of Navarra (UNAV), Pamplona, Spain.

Liver cirrhosis results from chronic hepatic damage and is characterized by derangement of the organ architecture with increased liver fibrogenesis and defective hepatocellular function. It frequently evolves into progressive hepatic insufficiency associated with high mortality unless liver transplantation is performed. We have hypothesized that the deficiency of critical nutrients such as essential omega-3 fatty acids might play a role in the progression of liver cirrhosis. Read More

Biochim Biophys Acta Mol Cell Res 2019 Apr 5;1866(4):588-597. Epub 2019 Jan 5.

Beijing Institute of Biotechnology, Beijing 100850, China. Electronic address:

Increased GP73 expression in hepatocytes from patients with acute hepatitis, through disease progression to cirrhosis and chronic liver disease suggests that progressive tissue remodeling and fibrogenesis are driving forces for GP73 upregulation. Nevertheless, details about regulation of GP73 expression and its biological functions remain elusive and await further characterization. In this study, we demonstrate that GP73 is a direct target of TGF-β1 transcriptional regulation. Read More

EBioMedicine 2019 Jan 2;39:484-496. Epub 2019 Jan 2.

OsteoNeuroGenInc, Seoul 08501, Republic of Korea. Electronic address:

Background: Myofibroblasts are known to play a key role in the development of idiopathic pulmonary fibrosis (IPF). Two drugs, pirfenidone and nintedanib, are the only approved therapeutic options for IPF, but their applications are limited due to their side effects. Thus, curative IPF drugs represent a huge unmet medical need. Read More

J Biol Chem 2019 Jan 4. Epub 2019 Jan 4.

Gastroenterology and Hepatology, Mayo Clinic, United States.

Transforming growth factor β (TGFβ) potently activates hepatic stellate cells (HSCs), which promotes production and secretion of extracellular matrix (ECM) proteins and hepatic fibrogenesis. Increased ECM synthesis and secretion in response to TGFβ is associated with endoplasmic reticulum (ER) stress and the unfolded protein response (UPR). TGFβ and UPR signaling pathways are tightly intertwined during HSC activation, but the regulatory mechanism that connects these two pathways is poorly understood. Read More

Nat Commun 2019 01 2;10(1). Epub 2019 Jan 2.

Centre for Inflammation and Tissue Repair, UCL Respiratory, Rayne Building, University College London, London, WC1E 6JF, UK.

Myofibroblasts are the key effector cells responsible for excessive extracellular matrix deposition in multiple fibrotic conditions, including idiopathic pulmonary fibrosis (IPF). The PI3K/Akt/mTOR axis has been implicated in fibrosis, with pan-PI3K/mTOR inhibition currently under clinical evaluation in IPF. Here we demonstrate that rapamycin-insensitive mTORC1 signaling via 4E-BP1 is a critical pathway for TGF-β stimulated collagen synthesis in human lung fibroblasts, whereas canonical PI3K/Akt signaling is not required. Read More

PLoS One 2019 2;14(1):e0208958. Epub 2019 Jan 2.

Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, Chapel Hill, North Carolina, United States of America.

Hepatic fibrosis develops from a series of complex interactions among resident and recruited cells making it a challenge to replicate using standard in vitro approaches. While studies have demonstrated the importance of macrophages in fibrogenesis, the role of Kupffer cells (KCs) in modulating the initial response remains elusive. Previous work demonstrated utility of 3D bioprinted liver to recapitulate basic fibrogenic features following treatment with fibrosis-associated agents. Read More

J Clin Invest 2019 Jan 2;129(1):24-33. Epub 2019 Jan 2.

Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.

Fibrosis, the progressive accumulation of connective tissue that occurs in response to injury, causes irreparable organ damage and may result in organ failure. The few available antifibrotic treatments modify the rate of fibrosis progression, but there are no available treatments to reverse established fibrosis. Thus, more effective therapies are urgently needed. Read More

Mol Ther Nucleic Acids 2018 Nov 20;14:114-130. Epub 2018 Nov 20.

Department of Orthopaedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China; Department of Orthopaedics, Shanghai Sixth People's Hospital East Affiliated to Shanghai University of Medicine & Health Sciences, Shanghai 201306, China. Electronic address:

Following tendon injury, the development of fibrotic healing response impairs tendon function and restricts tendon motion. Peritendinous tissue fibrosis poses a major clinical problem in hand surgery. Communication between macrophages and tendon cells has a critical role in regulating the tendon-healing process. Read More

Life Sci 2019 Mar 22;220:194-200. Epub 2018 Dec 22.

Department of Dermatology, Xiangya Hospital, Central South University, Changsha 410008, China; Hunan Key Laboratory of Skin Cancer and Psoriasis, Xiangya Hospital, Central South University, Changsha 410008, China; Hunan Engineering Research Center of Skin Health and Disease, Xiangya Hospital, Central South University, Changsha 410008, China. Electronic address:

Lysophosphatidic acid (LPA) is the simplest phospholipid found in nature. LPA is mainly biosynthesized in tissues and cells by autotoxin and PA-PLA1α/PA-PLA1β and is degraded by lipid phosphate phosphatases (LPPs). It is an important component of biofilm, an extracellular signal transmitter and intracellular second messenger. Read More

J Pathol 2018 Dec 25. Epub 2018 Dec 25.

Department of Imaging and Pathology, KU Leuven and University Hospitals Leuven, Leuven, Belgium.

Ductular reaction (DR) represents the activation of hepatic progenitor cells (HPCs) and has been associated with features of advanced chronic liver disease; yet it is not clear whether these cells contribute to disease progression and how the composition of their micro-environment differs depending on the aetiology. This study aimed to identify HPC-associated signalling pathways relevant in different chronic liver diseases using a high-throughput sequencing approach. DR/HPCs were isolated using laser microdissection from patient samples diagnosed with HCV or primary sclerosing cholangitis (PSC), as models for hepatocellular or biliary regeneration. Read More

J Pathol 2018 Dec 23. Epub 2018 Dec 23.

Departament de Bioquímica i Biologia Molecular, Institut de Biomedicina de la Universitat de Barcelona (IBUB), Universitat de Barcelona, Barcelona, Spain.

FGF21 is an endocrine factor that contributes to multiple pathophysiological processes, mainly via its action as a metabolic regulator and cardioprotective agent. Recent studies have shown increased circulating FGF21 levels in hypertensive patients and in mouse models of hypertension. However, the relevance of FGF21 in hypertensive heart disease has not been addressed. Read More

J Adv Res 2019 Jan 30;15:49-58. Epub 2018 Aug 30.

Department of Orthopaedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai 200233, China.

The dysregulation of long non-coding RNAs (lncRNAs) is associated with the development of various diseases. However, little is known about the regulatory function of lncRNAs in peritendinous fibrosis. Therefore, the expression profiles of lncRNAs and mRNAs in normal tendon and fibrotic peritendinous tissues were analyzed in this study using RNA sequencing. Read More

FASEB J 2018 Dec 21:fj201801976R. Epub 2018 Dec 21.

Gastroenterology Division, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.

Liver fatty acid binding protein (L-Fabp) modulates lipid trafficking in enterocytes, hepatocytes, and hepatic stellate cells (HSCs). We examined hepatocyte vs. HSC L-Fabp deletion in hepatic metabolic adaptation and fibrotic injury. Read More