Effect of Hepatocyte Growth Factor-Transfected Human Umbilical Cord Mesenchymal Stem Cells on Hepatic Stellate Cells by Regulating Transforming Growth Factor-β1/Smads Signaling Pathway

Abstract

Studies have shown that human umbilical cord mesenchymal stem cells (hUCMSCs) could ameliorate liver fibrosis (LF) through inhibiting the activation of hepatic stellate cells (HSCs). However, the specific mechanisms have not been studied clearly. The purpose of this study was to explore the possible mechanism of hepatocyte growth factor (HGF)-transfected hUCMSCs in inhibiting the proliferation and activation of HSCs-T6. The upper and lower double-cell coculture system was established among HGF-hUCMSCs, LV5-NC-hUCMSCs, hUCMSCs, and HSCs-T6 in experimental groups; HSCs-T6 were cultured alone as control group. After coculturing for 1, 2, and 3 days, results showed that HGF-transfected hUCMSCs could decrease cell viability of HSCs-T6 and promote apoptosis; inhibit their activation and reduce the expression of Collagen I, Collagen III, TGF-β1, Smad2 and Smad3, which may be related to inhibiting the activation of TGF-β1/Smads signaling pathway. These findings suggested that HGF-transfected hUCMSCs may be used as an alternative and novel therapeutic approach for the treatment of LF.

Keywords: HGF; TGF-β1/Smads signaling pathway; coculture; hepatic stellate cells-T6; human umbilical cord mesenchymal stem cells; liver fibrosis.