Influence of hepatocyte growth factor-transfected bone marrow-derived mesenchymal stem cells towards renal fibrosis in rats.

BACKGROUND & OBJECTIVES: Hepatocyte growth factor (HGF) produced by endothelial cells, fibroblasts, fat cells and other interstitial cells, can promote angiogenesis, repair damaged tissues and resist fibrosis. Mesenchymal stem cells (MSCs) are located in bone marrow and secrete a variety of cytokines and are often used in the repair and regeneration of damaged tissues. This study was aimed to investigate the influence of HGF-transfected bone marrow-derived MSCs towards renal fibrosis in rats.

METHODS

The HGF gene-carrying adenoviral vector (Ad-HGF) was transfected into MSCs, and the Ad-HGF-modified MSCs were transplanted into rats with unilateral ureteral obstruction (UUO). The localization of renal transplanted cells in the frozen section was observed with fluorescence microscope. The Masson's trichrome staining was performed to observe the renal collagen deposition, and the immunohistochemistry was performed to detect the expressions of α-smooth muscle actin (α-SMA) and HGF in renal tissues. Reverse transcription (RT)-PCR was used to detect the mRNA expressions of α-SMA, HGF and fibronectin (FN).

RESULTS

Ad-HGF-modified MSCs could highly express HGF in vitro. On the post-transplantation 3, 7 and 14 day, the 4',6-diamidino-2-phenylindole (DAP)-labelled transplanted cells were seen inside renal tissues. Compared with UUO group, the renal collagen deposition in transplantation group was significantly reduced, and the expressions of α-SMA mRNA and protein were significantly decreased, while the expressions of HGF mRNA and protein were significantly increased, and the expression of FN mRNA was significantly decreased (P<0.001).

INTERPRETATION & CONCLUSIONS: Trans-renal artery injection of HGF-modified MSCs can effectively reduce the renal interstitial fibrosis in UUO rat model.