Bone Morphogenetic Protein-7 Inhibits Epithelial-mesenchymal Transition Induced by Silica through Smad Pathway
Bone morphogenetic protein-7 (BMP-7) has been shown to inhibit liver and renal fibrosis in vivo and in vitro studies.There is no study to investigate BMP-7s role in the development of pulmonary fibrosis induced by silica.In the current study, we used the rat model to explore the potential antifibrotic role of BMP-7 and its underlying mechanism in silica-induced pulmonary fibrosis.Sixty Wistar rats were randomly assigned into three groups.Control group received saline, silica group received silica and BMP-7 treated group received silica and BMP-7.BMP-7 was administered to silica-treated rats intraperitoneally at a dose of 300 μg/kg/injection from day 8 to day 30 every other day.After the animals were sacrificed on day 15 and 30,hydroxyproline levels, the protein expressions of BMP/Smad and TGF-β/Smad signaling,Immunohistochemistry and histopathology in lung tissues were analyzed.The hydroxyproline contents in BMP-7 treated groups were significantly lower than the silica groups (P<0.05).Histopathological results showed BMP-7 could reduce the progression of silica induced fibrosis.lmmunohistochemical findings demonstrated the potential of BMP-7 to inhibit silica induced EMT in a rat model of pulmonary fibrosis.Furthermore, the expression of p-Smad1/5/8, a marker of BMP/Smad signaling, was significantly up-regulated in BMP-7 treated groups (P<0.05)compared with the silica groups.On the contrary, the expression of p-Smad2/3, a marker for TGF-β/Smad signaling, reduced significantly in BMP-7-treated groups compared with silica groups (P<0.05).in conclusion, the pulmonary fibrosis and EMT induced by silica in rats was significantly reduced with the therapeutic treatment of BMP-7.The antifibrotic effect of BMP-7 could be related to the activation of BMP/Smad signaling and inhibition of TGF-β/Smad pathways.Our studies provide supportive evidence for the potential of BMP-7 in therapy of silicosis.
Occupational health Silicosis Epithelial-mesenchymal transition Bone morphogenetic protein-7 Smad signal pathway
Gengxia Yang Zhonghui Zhu Yan Wang Ai Gao Piye Niu Lin Tian
国际会议
北京
英文
18-31
2013-06-01（万方平台首次上网日期，不代表论文的发表时间）