Xiao-Hua Zhang1, Yong Chen1, Bin Li1, Ji-Yong Liu1, Chong-Mei Yang1, Ming-Ze Ma2. 1. Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong University Jinan, Shandong Province, China. 2. Department of Infectious Diseases, Shandong Provincial Hospital Affiliated to Shandong University Jinan, Shandong Province, China.
Abstract
AIM: To elucidate the effect of inhibiting follistatin-like 1 on liver fibrosis and activation of hepatic stellate cells in mice. METHODS: We generated a follistatin-like 1 neutralizing antibody that can inhibit TGF-β 1-induced expression of collagen1α1 in primary mouse liver fibroblasts. All of the mice in our study were induced with carbon tetrachloride and thioacetamide. In addition, primary hepatic stellate cells from mice were isolated from fresh livers using density gradient separation. The degree and extent of fibrosis in mouse livers from the different groups were evaluated by Sirius Red and Masson staining. The effect of the follistatin-like 1 neutralizing antibody on proliferation and migration of hepatic stellate cells was detected using CCK-8 and Transwell assays, respectively. RESULTS: Expression of follistatin-like 1 in human cirrhotic liver tissue was higher than that in normal liver tissue. Blocking follistatin-like 1 resulted in a delay of primary hepatic stellate cell activation and down-regulation of the migratory capacity of hepatic stellate cells. Blocking follistatin-like 1 also down-regulated TGF-beta signaling in primary hepatic stellate cells from mice. Finally, inhibition of follistatin-like 1 attenuated liver fibrosis and liver function damage in vivo. CONCLUSIONS: Inhibiting follistatin-like 1 attenuates liver fibrosis and causes a delay in hepatic stellate cell activation. The effect of follistatin-like 1 on liver fibrosis is mainly attributed to its role in regulating TGF-beta signaling. IJCEP
AIM: To elucidate the effect of inhibiting follistatin-like 1 on liver fibrosis and activation of hepatic stellate cells in mice. METHODS: We generated a follistatin-like 1 neutralizing antibody that can inhibit TGF-β 1-induced expression of collagen1α1 in primary mouse liver fibroblasts. All of the mice in our study were induced with carbon tetrachloride and thioacetamide. In addition, primary hepatic stellate cells from mice were isolated from fresh livers using density gradient separation. The degree and extent of fibrosis in mouse livers from the different groups were evaluated by Sirius Red and Masson staining. The effect of the follistatin-like 1 neutralizing antibody on proliferation and migration of hepatic stellate cells was detected using CCK-8 and Transwell assays, respectively. RESULTS: Expression of follistatin-like 1 in humancirrhotic liver tissue was higher than that in normal liver tissue. Blocking follistatin-like 1 resulted in a delay of primary hepatic stellate cell activation and down-regulation of the migratory capacity of hepatic stellate cells. Blocking follistatin-like 1 also down-regulated TGF-beta signaling in primary hepatic stellate cells from mice. Finally, inhibition of follistatin-like 1attenuated liver fibrosis and liver function damage in vivo. CONCLUSIONS: Inhibiting follistatin-like 1 attenuates liver fibrosis and causes a delay in hepatic stellate cell activation. The effect of follistatin-like 1 on liver fibrosis is mainly attributed to its role in regulating TGF-beta signaling. IJCEP
Authors: Gopinath M Sundaram; John E A Common; Felicia E Gopal; Satyanarayana Srikanta; Krishnaswamy Lakshman; Declan P Lunny; Thiam C Lim; Vivek Tanavde; E Birgitte Lane; Prabha Sampath Journal: Nature Date: 2013-02-10 Impact factor: 49.962