Protective action of hepatocyte growth factor on transforming growth factor beta-1-induced alpha-smooth muscle actin and extracellular matrix in cultured human peritoneal fibroblasts
Dapeng Jiang, Changqing Xu, Zhaozhu Li, Yubo Zhang, Fuyou Han, Zhitao Jiang
Med Sci Monit 2010; 16(8): BR250-254
Available online: 2010-08-01
Background: Peritoneal adhesion is the leading cause of severe mechanical bowel obstruction, female infertility, pelvic pain, and difficult surgical procedures. TGF-beta1 plays an important role in matrix production associated with postoperative peritoneal adhesion development. Recent investigators have shown that HGF works on several organs and has been given widespread attention because it has proved to have strong antifibrotic activity. The aim of this study was to determine the impact of HGF on markers of adhesion formation induced by TGF-beta1 in human peritoneal fibroblasts.
Material/Methods: Fibroblasts were collected from normal peritoneum and were cultured with 5 ng/ml of TGF-beta1 along with increasing doses of HGF (10–40 ng/ml). Expression of α-SMA was assessed by Western blot. The productions of collagen I and fibronectin in supernatants culture were examined by enzyme-linked immunosorbent assay (ELISA).
Results: TGF-beta1 significantly stimulated α-SMA, collagen I and fibronectin production in peritoneal fibroblasts. Remarkably, the addition of HGF reduced production of all components induced by TGF-beta1 in a dose-dependent manner.
Conclusions: This study suggests that HGF may be a novel, highly efficacious agent in the minimization of intra-abdominal adhesion. Although further studies are needed to assess the mechanisms of HGF in neutralizing the effect of TGF-beta1, these findings also provide a cellular and molecular basis for the action of HGF as an anti-adhesion agent.
Keywords: Peritoneum - cytology, Protective Agents - pharmacology, Hepatocyte Growth Factor - pharmacology, Fibronectins - biosynthesis, Fibroblasts - metabolism, Extracellular Matrix - metabolism, Collagen Type I - biosynthesis, Cells, Cultured, Adult, Actins - metabolism, Transforming Growth Factor beta1 - pharmacology