Mesenchymal Stem Cells Suppress TGF-β Release to Decrease α-SMA Expression in Ameliorating CCl4-Induced Liver Fibrosis

INTRODUCTION: Liver fibrosis (LF) is the excessive deposition of extracellular matrix (ECM), produced by overactivated hepatic stellate cells, following prolonged transforming growth factor-β (TGF-β) stimulation. The ability of mesenchymal stem cells (MSCs) to improve LF has been reported. However, the mechanisms of MSCs to ameliorate LF through suppressing TGF-β and α-smooth muscle actin (α-SMA) remains unclear. AIM: To investigate the effects of MSCs treatment on suppressing TGF-β levels and decreasing α-SMA expression in an LF model. METHODS: In this study, wenty-four male Wistar rats were injected intraperitoneal (IP) with carbon tetrachloride (CCL4), twice weekly, for eight weeks, to induce LF. Rats were randomly assigned to six groups: Sham, Control, Sham-lo, Sham-hi, and MSC-treated groups, at doses of 1 x 10(6) (T1) and 2x10(6) (T2) cells. TGF-β levels were analyzed by enzyme-linked immunosorbent assay (ELISA), whereas α-SMA expression was determined by immunohistochemistry staining. RESULTS: MSCs decreased the expression of TGF-β in T1 and T2 groups on day 3 and 14. The T2 group showed lower TGF-β levels than that in the T1 group. This finding was in line with the observed decrease in α-SMA expression and the number of collagen. CONCLUSION: MSCs treatment ameliorated LF by suppressing TGF-β production, leading to decreased α-SMA expression in a CCL4-induced LF animal model.