Effect of hepatocyte growth factor on peritoneal remodeling on chlorhexidine gluconate (CH) - induced peritoneal sclerosis in mice

Abstract

Objective : Characteristic peritoneal alterations in long-term peritoneal dialysis (PD) patients include loss of mesothelial cells and marked submesothelial fibrotic thickening with severe vasculopathy. Although cessation of PD treatment may induce functional and morphologic alterations of the peritoneum in long-term PD patients, controversial results concerning prognosis after cessation of PD treatment have been reported. Hepatocyte growth factor (HGF) is a well-known inducer of tissue remodeling and an anti-fibrotic factor. The present study examined serial morphologic changes in injured peritoneum after cessation of intraperitoneal chlorhexidine gluconate (CH) injection and the role of HGF in peritoneal remodeling in mice with CH-induced peritoneal sclerosis (PS). Methods : Fifty-seven male BL/6 mice were intraperitoneally injected for 2 /days with 0.5ml of 15 % ethanol dissolved in saline as a control or with 0.5ml of CH containing 15 % ethanol dissolved in saline as the CH group. The mice were sacrificed and the parietal peritoneum was harvested on days 0, 7, 21 and 35 after the final CH injection. Peritoneal tissues were also examined immunohistologically. Results : Severely fibrotic thickened peritoneum with marked angiogenesis recovered to almost normal after cessation of CH administration in PS mice. However, peritoneal remodeling was not observed linearly over time. The thickened peritoneum and increase in infiltrating monocytes persisted for 21 days at the peak of HGF expression in the peritoneum. After a marked increase in HGF expression, tissue remodeling rapidly progressed, and injured peritoneum had recovered to almost normal at day 35 in CH-induced peritoneal fibrosis mice. Conclusion : It appears that cessation of peritoneal dialysis may allow tissue repair via activation of HGF expression in the peritoneum. Stimulation of intrinsic HGF production in the peritoneum may be an important strategy for human encapsulating peritoneal sclerosis (EPS).