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Poly(ADP-ribose) polymerase-1 in high glucose-induced epithelial-mesenchymal transition during peritoneal fibrosis.

Abstract
Peritoneal fibrosis is a major complication of continuous ambulatory peritoneal dialysis (CAPD). The present study tested the hypothesis that ADP-ribose polymerase-1 (PARP-1) may play a role in peritoneal epithelial-mesenchymal transition and fibrosis under high glucose conditions. High glucose (126 mmol/l)-induced peritoneal EMT and fibrosis via the PARP-1 mechanism was examined in the primary culture of rat peritoneal mesothelial cells (PMCs) and in the human peritoneal mesothelial cell line (HMrSv5) in the presence or absence of a PARP-1 inhibitor PJ34 (3x10-6 M) or by knocking down PARP-1 with the PARP-1 siRNA technique. High glucose significantly increased PARP-1 expression and EMT as demonstrated by de novo expression of a mesenchymal marker α-SMA and loss of epithelial phenotype E-cadherin by both rat and human PMC, resulting in peritoneal fibrosis including up-regulation of plasminogen activator inhibitor-1 (PAI-1), collagen I, and fibronectin mRNA and protein expression. All these fibrotic responses induced by high glucose were significantly inhibited by the PARP-1 inhibitor PJ34 (all P<0.05) or by knocking down PARP-1 with the siRNA technique. Results from this study suggested that high glucose stimulates peritoneal EMT and fibrosis via a PARP-1-dependent mechanism, and targeting the PARP-1 may represent an alternative therapeutic potential for CAPD-related peritoneal fibrosis.
AuthorsPing Lei, Zongpei Jiang, Hengmei Zhu, Xiaoyan Li, Ning Su, Xueqing Yu
JournalInternational journal of molecular medicine (Int J Mol Med) Vol. 29 Issue 3 Pg. 472-8 (Mar 2012) ISSN: 1791-244X [Electronic] Greece
PMID22159350 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Plasminogen Activator Inhibitor 1
  • Poly(ADP-ribose) Polymerases
  • Glucose
Topics
  • Animals
  • Cells, Cultured
  • Epithelial Cells (drug effects, metabolism)
  • Epithelial-Mesenchymal Transition (drug effects)
  • Extracellular Matrix (genetics, metabolism)
  • Gene Expression Regulation (drug effects)
  • Glucose (pharmacology)
  • Humans
  • Male
  • Peritoneal Fibrosis (enzymology, genetics)
  • Plasminogen Activator Inhibitor 1 (genetics, metabolism)
  • Poly(ADP-ribose) Polymerases (genetics, metabolism)
  • Rats
  • Rats, Sprague-Dawley

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