BMSCs protect against liver injury via suppressing hepatocyte apoptosis and activating TGF-β1/Bax singling pathway

Abstract

Many factors cause liver injury, including chronic consumption of alcohol, irregular use of drugs, excessive levels of arsenic in water. This study aims to investigate role of bone marrow-derived mesenchymal stem cells (BMSCs) in liver injury recovery and to explore mechanism. BMSCs and primary hepatocytes were isolated, cultured and identified. Hepatocyte model and hepatic fibrosis (HF) model were established using carbon tetrachloride (CCL-4). The role of BMSCs were investigated in both in vitro and in vivo levels. Cell proliferation was examined using MTT assay. Transforming growth factor-β1 (TGF-β1), Bcl-2 and Bax expression were detected using western blot and real-time PCR, respectively. Results indicated that BMSCs and primary hepatocytes were successfully isolated and identified, and hepatocyte model was successfully established. BMSCs and HGF treatment enhance viability of normal hepatocytes and hepatocyte injury model. Cell viability in BMSCs treatment and Bax-1 inhibitor treatment group was higher significantly compared to normal hepatocyte control and injury hepatocyte model, respectively (P<0.05). Bax-1 expression was significantly lower and Bcl-2 was significantly higher in Bax-1 inhibitor treatment and BMSCs treatment group compared to normal hepatocyte control (normal rats) and injury hepatocyte model (HF model), respectively (P<0.05). BMSCs significantly decreased ALT and AST levels compared to Saline group (P<0.05). In conclusion, function of BMSCs in liver injury was triggered by inhibiting hepatocyte apoptosis and leading cell proliferation through TGF-β1/Bax singling pathway. Our study proved protective role of BMSCs against liver injury via TGF-β1/Bax pathway, which would enrich application of BMSC in clinical.