title: Inhibition of Rho-kinase alleviates peritoneal fibrosis and angiogenesis in a rat model of peritoneal dialysis.
abstract: OBJECTIVE
  The present study investigated whether Rho-kinase inhibition had a therapeutic role on the pathogenesis of peritoneal fibrosis and angiogenesis.
  
  
  METHODS
  A rat model of peritoneal dialysis was induced by a daily intraperitoneal infusion of 4.25% Dianeal. Those rats were treated with Rho-kinase inhibitor, fasudil. Immunofluorescence, Western blot and RT-PCR were used to detect the expression of TGF-β1, Collagen I, αSMA and VEGF in each group. Microvessel density (MVD) was measured by immunohistochemistry. Rho-kinase activity was determined by western immunoblotting.
  
  
  RESULTS
  Rho-kinase was activated in the peritoneum of the PD group, which was inhibited by fasudil. Compared with PD group, the mRNA and protein expressions of TGF-β1, αSMA and Collagen I were significantly downregulated in fasudil treatment groups in a dose-dependent manner, and the expression of VEGF and peritoneal MVD was also significantly downregulated in fasudil treatment groups in a dose-dependent manner.
  
  
  CONCLUSIONS
  The Rho-kinase was activated in the peritoneum of the peritoneal dialysis rats, and the inhibition of Rho-kinase by fasudil can remarkably decrease peritoneal fibrosis and angiogenesis.
authors.affiliation: Department of Nephrology, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Weisheng
authors.initials: W
authors.lastname: Peng
authors.forename: Qiaoling
authors.initials: Q
authors.lastname: Zhou
authors.forename: Xiang
authors.initials: X
authors.lastname: Ao
authors.forename: Rong
authors.initials: R
authors.lastname: Tang
authors.forename: Zhou
authors.initials: Z
authors.lastname: Xiao
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000199:Actins / Q000378:metabolism; D000818:Animals; D024042:Collagen Type I / Q000378:metabolism; D015314:Dialysis Solutions / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D055806:Microvessels / Q000187:drug effects / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D010530:Peritoneal Dialysis / Q000009:adverse effects*; D056627:Peritoneal Fibrosis / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D010537:Peritoneum / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000199:Actins; D024042:Collagen Type I; D015314:Dialysis Solutions; D047428:Protein Kinase Inhibitors; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A; D054460:rho-Associated Kinases; C498862:Acta2 protein, rat; C049347:fasudil