Anti-fibrotic effects of bone morphogenetic protein-7-modified bone marrow mesenchymal stem cells on silica-induced pulmonary fibrosis
Anti-fibrotic effects of bone morphogenetic protein-7-modified bone marrow mesenchymal stem cells on silica-induced pulmonary fibrosis
复制标题
骨形态发生蛋白7修饰的骨髓间充质干细胞对二氧化硅诱导的肺纤维化的抗纤维化作用
DOI：
10.1016/j.yexmp.2016.12.010
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发表时间：
2017-02-01
影响因子：
3.6
通讯作者：
Tian, Lin
中科院分区：
文献类型：
--
作者：
Li, Xiaoli;An, Guoliang;Tian, Lin
矽肺是一种职业性肺病，由暴露于结晶二氧化硅的小颗粒引起，最终导致弥漫性肺纤维化。有证据表明骨形态发生蛋白-7（BMP-7）和骨髓间充质干细胞（BMSCs）在肺部疾病中具有抗纤维化作用。因此，结合基因工程和干细胞生物学的策略可能具有治疗严重损伤和疾病的巨大潜力。因此，我们通过慢病毒转导修饰BMSCs以过表达BMP-7基因（BMP-7-BMSCs），然后评估这些细胞是否在体内抑制纤维化过程。Wistar大鼠分为4组：对照组、二氧化硅组、BMSCs组和BMP-7-BMSCs组。对照组给予生理盐水，二氧化硅组给予二氧化硅和生理盐水，BMSCs组给予二氧化硅和BMSCs，BMP-7-BMSCs组给予二氧化硅和BMP-7-BMSCs。在二氧化硅滴注后第15或30天处死大鼠。组织学检查采用苏木精-伊红染色和Masson三色染色。通过羟脯氨酸、纤连蛋白（FN）和转化生长因子（TGF）-β 1的水平评价纤维化的严重程度。肺泡上皮细胞的恢复通过上皮标志物表面活性蛋白（SP）-C和水通道蛋白（AQP）-5来检测。组织学结果显示，BMP-7-BMSCs能显著阻断二氧化硅诱导的纤维化进程。BMP-7-BMSCs组羟脯氨酸、FN和TGF-β 1含量明显低于BMSCs组（P
Silicosis is an occupational lung disease caused by exposure to small particles of crystalline silica, which ultimately results in diffuse pulmonary fibrosis. Evidence indicates an anti-fibrotic role of bone morphogenetic protein-7 (BMP-7) and bone marrow mesenchymal stem cells (BMSCs) in lung diseases. Therefore, strategies incorporating genetic engineering and stem cell biology might have a tremendous potential to treat critical injuries and diseases. Therefore, we modified BMSCs to overexpress the BMP-7 gene (BMP-7-BMSCs) by lentivirus transduction, and then evaluated whether fibrotic processes were inhibited by these cells in vivo. Wistar rats were divided into four groups: control, silica, BMSCs, and BMP-7-BMSCs. The control group received saline, the silica group received silica and saline, the BMSCs group received silica and BMSCs, and the BMP-7-BMSCs group received silica and BMP-7-BMSCs. Rats were sacrificed on days 15 or 30 after silica instillation. Hematoxylin and eosin, and Masson's trichrome staining were performed for histological examination. The severity of fibrosis was evaluated by the levels of hydroxyproline, fibronectin (FN), and transforming growth factor (TGF)-beta 1. Restoration of the alveolar epithelium was detected by the epithelial marker surfactant protein (SP)-C and aquaporin (AQP)-5. Histopathological results showed that BMP-7-BMSCs could remarkably block the progression of silica-induced fibrosis. Hydroxyproline, FN, and TGF-beta 1 contents in the BMP-7-BMSCs-treated group were significantly lower than those in the BMSCs group (P