Bone morphogenetic protein-7 represses hepatic stellate cell activation and liver fibrosis via regulation of TGF-β/Smad signaling pathway

Figure 5 Exogenous bone morphogenetic protein 7 ameliorates liver fibrosis in carbon tetrachloride-induce mice model and bone morphogenetic protein 7 activation is abnormally changed in patient liver tissues. Mice were challenged with carbon tetrachloride (CCl₄) or corn oil (Control), followed by intraperitoneal injection of BMP7 (100 ng/g, three times per week for 4 wk) or 0.9% saline (Vehicle) as described in Materials and Methods. The severity of liver fibrosis was evaluated. A: Masson staining (100 ×). B: Morphometric analysis of fibrotic lesions in liver. C: Western blot analysis of expression of α-SMA and Col I. Equivalent amount of whole liver detergent lysates were blotted with the indicated antibodies. Each lane represents one individual mouse. GAPDH was used as a loading control. D: Densitometry analysis of the effect of BMP7 on myofibroblast differentiation (alpha-smooth muscle actin), extracellular matrix production (collagen I). Data are pooled and represented as the mean ± SE, n = 8 animals per group. ^bP < 0.01. E: Representative sections of Masson staining (100×) from paraffin-embedded sections of normal, fibrotic, and cirrhotic human liver tissues and Western blot analysis of expression of BMP7. Equivalent amount of whole liver detergent lysates were blotted with the BMP7 antibody. Each lane represents one individual person. GAPDH was used as a loading control. F: Densitometry analysis of BMP7 activation in indicated liver tissues. ^bP < 0.01. BMP7: Bone morphogenetic protein 7; Col I: Collagen I; α-SMA: Alpha-smooth muscle actin; CCl_4: Carbon tetrachloride.