Bone morphogenetic protein-7 inhibits silica-induced pulmonary fibrosis in rats
Bone morphogenetic protein-7 inhibits silica-induced pulmonary fibrosis in rats
复制标题
骨形态发生蛋白7抑制二氧化硅诱导的大鼠肺纤维化
DOI：
10.1016/j.toxlet.2013.04.017
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发表时间：
2013-07-04
影响因子：
3.5
通讯作者：
Tian, Lin
中科院分区：
文献类型：
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作者：
Yang, Gengxia;Zhu, Zhonghui;Tian, Lin
骨形态发生蛋白-7（BMP-7）已在体内和体外研究中显示出抑制肝和肾纤维化。目前还没有研究探讨BMP-7在二氧化硅诱导的肺纤维化发展中的作用。在本研究中，我们使用大鼠模型来探讨BMP-7在二氧化硅诱导的肺纤维化中的潜在抗纤维化作用及其潜在机制。60只Wistar大鼠随机分为3组。对照组接受生理盐水，二氧化硅组接受二氧化硅，BMP-7治疗组接受二氧化硅和BMP-7。从第8天到第30天，每隔一天以300 μ g/kg/注射的剂量向二氧化硅处理的大鼠腹膜内施用BMP-7。分别于第15天和第30天处死动物，检测肺组织羟脯氨酸水平、BMP/Smad和TGF-β/Smad信号通路蛋白表达及组织病理学改变。BMP-7处理组的羟脯氨酸含量显著低于二氧化硅处理组（P < 0.05）。组织学结果显示，BMP-7可减缓二氧化硅诱导的纤维化进程。BMP-7处理组p-Smad 1/5/8的表达较SiO2处理组显著上调（P < 0.05）。BMP-7处理组TGF-β/Smad信号通路标志物p-Smad 2/3的表达明显低于二氧化硅处理组（P < 0.05）。总之，通过BMP-7的治疗性处理，大鼠中二氧化硅诱导的肺纤维化显著减少。BMP-7的抗纤维化作用可能与激活BMP/Smad信号通路和抑制TGF-β/Smad通路有关。(C)2013爱思唯尔爱尔兰有限公司版权所有。
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. (C) 2013 Elsevier Ireland Ltd. All rights reserved.