Mesenchymal Stem Cells Suppress Tgf-β Release to Decrease Α- Sma Expression in Ameliorating Ccl4-Induced Liver Fibrosis

Abstract Background: Liver fibrosis (LF) is the excessive deposition of extracellular matrix (ECM),produced by overactivated hepatic stellate cells, following prolonged transforming growth factor-β (TGF-b) stimulation.The ability of mesenchymal stem cells (MSCs) to improveLF has been reported. However, the mechanismsof MSCs to ameliorate LF through suppressing TGF-β and α-smooth muscle actin (a-SMA) remain unclear.In this study, we investigated the ability of MSCs to ameliorate LF by suppressing TGF-band a-SMA expression. Methods: Twenty-four,male, Wistar rats were injected intraperitoneal (IP) by with carbon tetrachloride (CCL 4 ),twice weekly, for eight weeks, to induce LF. Rats were randomly assigned to four groups: Sham, Control, and MSC-treated groups, at doses of 1´10 6 (T1) and 2´10 6 (T2) cells. TGF-blevels were analyzed by enzyme-linked immunosorbent assay (ELISA),whereas a-SMA expression was determined by immunohistochemistry staining. Results: This study showed that TGF-bconcentrations significantly decreased in all treatment groupsat day 3 and 14. The T2 group showed lower TGF-blevels than that in the T1 group. This finding was in line with the observed decreasesina-SMA expression andnumber of colagen. Conclusions: MSCs treatmentamelioratedLF by suppressing TGF-b production,leading to decreaseda-SMA expressionin a CCL 4 -induced LF animal model.