title: 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.
authors.affiliation: Department of Nephrology, The First Affiliated Hospital, Sun                     Yat-Sen University, Guangzhou 510080, P.R. China.
authors.forename: Ping
authors.initials: P
authors.lastname: Lei
authors.forename: Zongpei
authors.initials: Z
authors.lastname: Jiang
authors.forename: Hengmei
authors.initials: H
authors.lastname: Zhu
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Li
authors.forename: Ning
authors.initials: N
authors.lastname: Su
authors.forename: Xueqing
authors.initials: X
authors.lastname: Yu
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005109:Extracellular Matrix / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D008297:Male; D056627:Peritoneal Fibrosis / Q000201:enzymology* / Q000235:genetics; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D017395:Plasminogen Activator Inhibitor 1; D011065:Poly(ADP-ribose) Polymerases; D005947:Glucose