https://scholars.lib.ntu.edu.tw/handle/123456789/563357
標題: | Fibrin-Induced Epithelial-to-Mesenchymal Transition of Peritoneal Mesothelial Cells as a Mechanism of Peritoneal Fibrosis: Effects of Pentoxifylline | 作者: | CHENG-CHUNG FANG JENQ-WEN HUANG Shyu R.-S. CHUNG-JEN YEN Shiao C.-H. CHIH-KANG CHIANG REY-HENG HU TUN-JUN TSAI |
公開日期: | 2012 | 卷: | 7 | 期: | 9 | 來源出版物: | PLoS ONE | 摘要: | Excessive fibrin deposition in the peritoneum is thought to be involved in the development of encapsulating peritoneal sclerosis (EPS), an important cause of morbidity and mortality in peritoneal dialysis patients. We investigated fibrin-induced epithelial-to-mesenchymal transition (EMT) of peritoneal mesothelial cells (PMCs) as a possible mechanism of fibrin involvement in EPS. In vitro, fibrin overlay of PMCs altered their morphology; increased α-smooth muscle actin, fibronectin, fibroblast specific protein-1, and αvβ3 integrin expression; and decreased cytokeratin 18 and E-cadherin expression. Fibrin overlay also increased focal adhesion kinase and Src kinase phosphorylation. Fibrin-induced changes were inhibited by treating the cells with αvβ3 integrin antibody or pentoxifylline (PTX). In a rat model, intraperitoneal injection of Staphylococcus aureus and fibrinogen induced severe EPS features, which were attenuated by PTX treatment. PTX-treated rats also showed preserved peritoneal ultrafiltration function and lower concentrations of cytokines than the untreated rats. S. aureus- and fibrinogen-injected rats had higher percentage of cytokeratin-positive cells in the omentum fibrotic tissue than controls; this was also reduced by PTX treatment. Our results suggest that fibrin induces EMT of PMCs by engaging αvβ3 integrin and activating associated kinases. Our EPS animal model showed that fibrin-induced EMT was involved in the pathogenesis of peritoneal fibrosis and was inhibited by PTX. ? 2012 Fang et al. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84866367674&doi=10.1371%2fjournal.pone.0044765&partnerID=40&md5=ee76a8adb5667662873750be5b79df52 https://scholars.lib.ntu.edu.tw/handle/123456789/563357 |
ISSN: | 1932-6203 | DOI: | 10.1371/journal.pone.0044765 | SDG/關鍵字: | alpha smooth muscle actin; calvasculin; cytokeratin; cytokeratin 18; fibrin; fibrinogen; fibronectin; focal adhesion kinase; interleukin 1beta; interleukin 6; pentoxifylline; plasminogen activator inhibitor 1; protein tyrosine kinase; tissue plasminogen activator; transforming growth factor beta1; tumor necrosis factor alpha; uvomorulin; vasculotropin; vitronectin receptor; animal cell; animal experiment; animal model; animal tissue; article; cell count; cell structure; controlled study; disease model; enzyme activation; enzyme phosphorylation; epithelial mesenchymal transition; human; human cell; in vitro study; male; mesothelium cell; nonhuman; omentum; pathogenesis; pathophysiology; peritoneal fibrosis; peritoneum cell; protein expression; rat; Staphylococcus aureus; ultrafiltration; Animals; Blotting, Western; Cells, Cultured; Epithelial Cells; Epithelial-Mesenchymal Transition; Fibrin; Fluorescent Antibody Technique; Humans; Male; Pentoxifylline; Peritoneal Fibrosis; Peritoneum; Phosphorylation; Rats; Rats, Wistar; Animalia; Rattus; Staphylococcus aureus |
顯示於: | 毒理學研究所 |
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