Hepatocyte growth factor prevents peritoneal fibrosis in an animal model of encapsulating peritoneal sclerosis
Matsuoka, T.; Maeda, Y.; Matsuo, K.; Naiki, Y.; Tamai, Y.; Sakaguchi, M.; Hasegawa, H.; Funauchi, M.; Kanamaru, A.
Journal of Nephrology 21(1): 64-73
2008
ISSN/ISBN: 1121-8428 PMID: 18264938 Document Number: 622267
Background. Ultrafiltration failure associated with peritoneal fibrosis can lead patients to discontinue continuous ambulatory peritonea[ dialysis (CAPD). It has been reported that the reciprocal imbalance between transforming growth factor-betal (TGF-beta 1) and hepatocyte growth factor (HGF) is closely involved in the progression of tissue fibrosis. We previously showed that exogenous HGF restores the growth of human peritoneal mesothelial cells suppressed by a high concentration of D-glucose or TGF-beta 1. In this study, we examined whether constitutive exposure to HGF prevents peritoneal fibrosis in an animal model of encapsulating peritoneal sclerosis (EPS).Methods: To establish the model, a daily intraperitoneal injection of 0.1% chlorhexidine gluconate was given to male Wister rats for 35 days. Rat peritoneal mesothelial cells (RPMCs) transfected with full-length human HGF cDNA in an expression vector (pUCSR alpha/HGF) were injected into the peritoneal cavity of the rats. Thereafter, pathological changes to the peritoneal membrane were observed, and the effect on peritoneal ultrafiltration volume was examined.Results: In the model, microscopic examination revealed a progressive thickening of the submesothelial layer, and an increase in the number of capillary vessels. Peritoneal ultrafiltration volume was decreased. Interestingly, the pathological changes to the peritoneal membrane were reversed by the intraperitoneal injection of pUCSR alpha/HGF-transfected RPMCs. Furthermore, peritoneal ultrafiltration volume was increased.Conclusions: The constitutive production of HGF by pUCSRa/HGF-transfected RPMCs can improve peritoneal fibrosis resulting in an increase in peritoneal ultrafiltration volume. This approach may have clinical application.