Bone morphogenetic protein-7 inhibits silica-induced pulmonary fibrosis in rats

作者：Yang, Gengxia; Zhu, Zhonghui; Wang, Yan; Gao, Ai; Niu, Piye; Tian, Lin^*

来源：Toxicology Letters, 2013, 220(2): 103-108.

DOI：10.1016/j.toxlet.2013.04.017

• Bone morphogenetic protein-7
• Silica
• Pulmonary fibrosis
• Smad proteins

Bone morphogenetic protein-7 (BMP-7) has been shown to inhibit liver and renal fibrosis in in vivo and 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 mu g/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-beta/Smad signaling, 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. 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-beta/Smad signaling, reduced significantly in BMP-7-treated groups compared with silica groups (P < 0.05). In conclusion, the pulmonary fibrosis 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-beta/Smad pathways.

• 出版日期2013-7-4
• 单位首都医科大学