Li Xiaoli, Wang Yan, An Guoliang, Liang Di, Zhu Zhonghui, Lian Ximeng, Niu Piye, Guo Caixia, Tian Lin
School of Public Health, Capital Medical University, Beijing 100069, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China.
Beijing Children's Hospital, Capital Medical University, Beijing, China.
Toxicol Lett. 2017 Mar 15;270:96-107. doi: 10.1016/j.toxlet.2017.02.016. Epub 2017 Feb 21.
The purpose of this study was to investigate the anti-fibrotic effect and possible mechanism of bone marrow mesenchymal stem cells (BMSCs) in silica-induced lung injury and fibrosis in vivo and in vitro. In vivo, rats were exposed to 50mg/ml silica intratracheally. The rats were sacrificed on day 15 or day 30 after intravenous injection of BMSCs. Histopathological examination demonstrated that BMSCs decreased the blue areas of collagen fibers and the number of nodules. Alveolar epithelium was damaged by silica, but it was restored by BMSCs. In vitro, BMSCs co-cultured with RLE-6TN cells in 6-Transwell plates were evaluated to determine the possible mechanism. The results demonstrated that BMSCs downregulated the expression of collagen I and III. BMSCs reversed morphological abnormalities and reduced the proliferation of RLE-6TN cells. These data showed that BMSCs did not give rise to alveolar epithelial cells directly, while the levels of hepatocyte growth factor, keratinocyte growth factor and bone morphogenetic protein -7 increased and expression of tumor necrosis factor-α and transforming growth factor-β1 decreased in the 6TN+Silica+BMSCs group compared with the 6TN+Silica group. Our results revealed that BMSCs exerted anti-fibrotic effects on silica-induced pulmonary fibrosis, which might be associated with paracrine mechanisms rather than differentiation.
本研究旨在探讨骨髓间充质干细胞（BMSCs）在体内外二氧化硅诱导的肺损伤和纤维化中的抗纤维化作用及可能机制。在体内，大鼠经气管内注入50mg/ml二氧化硅。在静脉注射BMSCs后第15天或第30天处死大鼠。组织病理学检查表明，BMSCs减少了胶原纤维的蓝色区域和结节数量。肺泡上皮受到二氧化硅损伤，但被BMSCs修复。在体外，评估在6孔Transwell板中与RLE-6TN细胞共培养的BMSCs以确定可能机制。结果表明，BMSCs下调了I型和III型胶原的表达。BMSCs逆转了形态异常并减少了RLE-6TN细胞的增殖。这些数据表明，BMSCs不会直接产生肺泡上皮细胞，而与6TN+二氧化硅组相比，6TN+二氧化硅+BMSCs组中肝细胞生长因子、角质形成细胞生长因子和骨形态发生蛋白-7的水平升高，肿瘤坏死因子-α和转化生长因子-β1的表达降低。我们的结果显示，BMSCs对二氧化硅诱导的肺纤维化发挥抗纤维化作用，这可能与旁分泌机制而非分化有关。
