Inhibition of Rho-kinase alleviates peritoneal fibrosis and angiogenesis in a rat model of peritoneal dialysis.

Abstract

BACKGROUND/AIMS:

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.

CONCLUSION:

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: Weisheng Peng, Qiaoling Zhou, Xiang Ao, Rong Tang, Zhou Xiao
• Journal: Renal failure (Ren Fail) Vol. 35 Issue 7 Pg. 958-66 (Aug 2013) ISSN: 1525-6049 [Electronic] England
• PMID: 23859538 (Publication Type: Journal Article)

Chemical References

• Actins
• Collagen Type I
• Dialysis Solutions
• Protein Kinase Inhibitors
• Transforming Growth Factor beta1
• Vascular Endothelial Growth Factor A
• smooth muscle actin, rat
• 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
• rho-Associated Kinases
• fasudil

Topics

• 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine (analogs & derivatives, pharmacology)
• Actins (metabolism)
• Animals
• Collagen Type I (metabolism)
• Dialysis Solutions (pharmacology)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Gene Expression Regulation (drug effects)
• Male
• Microvessels (drug effects, pathology)
• Neovascularization, Pathologic (drug therapy, etiology, metabolism, physiopathology)
• Peritoneal Dialysis (adverse effects)
• Peritoneal Fibrosis (drug therapy, etiology, metabolism, physiopathology)
• Peritoneum (blood supply, drug effects, metabolism, pathology)
• Protein Kinase Inhibitors (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Transforming Growth Factor beta1 (metabolism)
• Treatment Outcome
• Vascular Endothelial Growth Factor A (metabolism)
• rho-Associated Kinases (antagonists & inhibitors, metabolism)