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

Figure 4 Bone morphogenetic protein 7 inhibits hepatic stellate cell migration and proliferation via promoting Smad1/5/8 and attenuating TGF-β1-Smad signaling. A: Exogenous BMP7 (100 ng/mL) reduced cell migration in a wound scratch heal assay. The scratch wounds were almost healed in the control but gaps remained in the BMP7 treated cells at 24 h. B: Data are pooled and shown as % of wound area covered by cells over the indicated hours, relative to that of uninfected wild type (WT) fibroblasts in dimethyl sulfoxide (DMSO) medium. C: Cell growth in the presence of BMP7 as measured by direct cell count. D: Cell proliferation measured by BrdU cell proliferation assay in the presence of BMP7. E: Western blot analysis of expression of p-Smad3, p-Smad1/5/8, and p-P38. HSCs were treated as in panel A and lysed at 24 h. Equivalent amount of whole cell detergent lysates were used for detection of phosphorylation of Smad3 (p-Smad3), phosphorylation of Smad1/5/8 (p-Smad1/5/8), and phosphorylation of P38 (p-P38). F: Densitometry analysis of the effect of BMP7 on p-Smad3, p-Smad1/5/8, and p-P38 activation at the indicated condition. Data are pooled from at least three independent experiments and represented as the mean ± SE. ^bP < 0.01. BMP7: Bone morphogenetic protein 7; p-Smad3: Phosphorylated Smad3; p-Smad1/5/8: Phosphorylated Smad1/5/8; TGF-β1: Transforming growth factor-beta 1; Col I: Collagen I; p-P38: Phosphorylated P38.