Smad7-overexpressing rat BMSCs inhibit the fibrosis of hepatic stellate cells by regulating the TGF-β1/Smad signaling pathway

Mesenchymal stem cells (MSCs) are able to differentiate into hepatocytes, promote the regeneration of hepatic cells and inhibit the progression of hepatic fibrosis. Transforming growth factor (TGF)-β1 is one of the key factors in the development of liver fibrosis, which also promotes extracellular matrix (ECM) formation. Drosophila mothers against decapentaplegic 7 (Smad7) is an essential negative regulator in the TGF-β1/Smad signaling pathway. In the present study, bone mesenchymal stem cells (BMSCs) were isolated from rat bone marrow and transfected with lentiviral vectors carrying the Smad7 gene. Smad7-enhanced green fluorescent protein (EGFP)-BMSCs stably expressing Smad7 were subsequently co-cultured with hepatic stellate cells (HSCs) for 48 h. Smad7 and TGF-β1 levels in the culture medium were detected using ELISA, and the levels of collagen (Col) I, Col III, laminin (LN) and hyaluronic acid (HA) were measured using immunoassays. The early apoptosis rates of HSCs were determined via flow cytometry. Reverse transcription-quantitative polymerase chain reaction and western blotting were performed to evaluate the mRNA and protein expression profiles, respectively. The results indicated that Smad7-EGFP-BMSCs stably expressing Smad7 were successfully constructed. Upon co-culturing with rat Smad7-EGFP-BMSCs, the early apoptotic rate of HSCs was significantly increased (P