Possible effects of hepatocyte growth factor for the prevention of peritoneal fibrosis.
OBJECTIVE
Some patients who had carried out long-term continuous ambulatory peritoneal dialysis discontinued the treatment because of progressive peritoneal fibrosis. It has been previously reported that transforming growth factor-beta1 (TGF-beta1) is one of the factors that induces peritoneal fibrosis. Also, hepatocyte growth factor (HGF) plays a role in the prevention of fibrosis and in inhibiting TGF-beta1 production. In this study, we examined the effects of HGF on peritoneal fibrosis by TGF-beta1 induced by high concentrations of D-glucose.


METHODS
We transfected a full-length human HGF cDNA in an expression vector into human peritoneal mesothelial cells (HPMCs) using the calcium phosphate method. Transfected HPMCs were cultured with high concentrations of D-glucose solution and co-cultured with fibroblasts using a transwell system. Cell proliferation was determined using the Tetra Color One method. TGF-beta1 and HGF protein were measured by enzyme-linked immunosorbent assay.


RESULTS
In addition to recombinant HGF, the growth inhibition of HPMCs by high concentration D-glucose or TGF-beta1 was significant. By transfecting HGF cDNA into HPMCs, growth inhibition by high concentration D-glucose was completely restored. Furthermore, the production of TGF-beta1 was also significantly decreased.


CONCLUSIONS
These results suggested that exogenous HGF could possibly prevent peritoneal fibrosis.
Matsuo
Koki
K
Department of Hematology, Kinki University School of Medicine, Osaka, Japan.
Maeda
Yasuhiro
Y
Naiki
Yoshito
Y
Matsuoka
Toshiaki
T
Tamai
Yoshihisa
Y
Yonekawa
Satoru
S
Sakaguchi
Mika
M
Iwamoto
Ichiro
I
Hasegawa
Hirohumi
H
Matsumoto
Kunio
K
Nakamura
Toshikazu
T
Kanamaru
Akihisa
A
D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D004847:Epithelial Cells / Q000187:drug effects; D005355:Fibrosis / Q000517:prevention & control*; D005947:Glucose / Q000494:pharmacology; D017228:Hepatocyte Growth Factor / Q000627:therapeutic use*; D006801:Humans; D009852:Omentum / Q000166:cytology; D010531:Peritoneal Dialysis, Continuous Ambulatory / Q000009:adverse effects*; D010537:Peritoneum / Q000473:pathology*; D011994:Recombinant Proteins / Q000627:therapeutic use; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000009:adverse effects / Q000378:metabolism; D053773:Transforming Growth Factor beta1
C066855:HGF protein, human; D011994:Recombinant Proteins; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D017228:Hepatocyte Growth Factor; D005947:Glucose