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-7”s 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.Immunohistochemical findings demonstrated the potential of BMP-7 to inhibit silica induced EMT in a rat model of pulmonary fibrosis.Furthermore, the expression of p-Smadl/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 Li Chen Lin Tian
Department of Occupational Health and Environmental Health, School of Public Health, Capital Medical University, Beijing 100069, China
国内会议
北京
英文
84-95
2013-11-01（万方平台首次上网日期，不代表论文的发表时间）