Hepatocyte growth factor prevents peritoneal fibrosis in an animal model of encapsulating peritoneal sclerosis.
BACKGROUND
Ultrafiltration failure associated with peritoneal fibrosis can lead patients to discontinue continuous ambulatory peritoneal dialysis (CAPD). It has been reported that the reciprocal imbalance between transforming growth factor-beta1 (TGF-beta1) 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-beta1. 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 (pUCSRalpha/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 pUCSRalpha/HGF-transfected RPMCs. Furthermore, peritoneal ultrafiltration volume was increased.


CONCLUSIONS
The constitutive production of HGF by UCSRalpha/HGF-transfected RPMCs can improve peritoneal fibrosis resulting in an increase in peritoneal ultrafiltration volume. This approach may have clinical application.
Matsuoka
Toshiaki
T
Department of Nephrology, and Rheumatology, Kinki University School of Medicine, Osaka, Japan.
Maeda
Yasuhiro
Y
Matsuo
Koki
K
Naiki
Yoshito
Y
Tamai
Yoshihisa
Y
Sakaguchi
Mika
M
Hasegawa
Hirofumi
H
Funauchi
Masanori
M
Kanamaru
Akihisa
A
D000818:Animals; D002710:Chlorhexidine / Q000031:analogs & derivatives / Q000633:toxicity; D004195:Disease Models, Animal; D005355:Fibrosis; D017228:Hepatocyte Growth Factor / Q000502:physiology*; D006801:Humans; D008297:Male; D010537:Peritoneum / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D012598:Sclerosis; D014162:Transfection; D014462:Ultrafiltration
C066855:HGF protein, human; D017228:Hepatocyte Growth Factor; C010882:chlorhexidine gluconate; D002710:Chlorhexidine