Basic Medical College, Hebei Medical Collage, Shijiazhuang, Hebei, 050017, China.
School of Public Health, Hebei Key Laboratory for Organ Fibrosis Research, North China University of Science and Technology, Tangshan, Hebei, 063210, China.
Exp Cell Res. 2020 Mar 15;388(2):111878. doi: 10.1016/j.yexcr.2020.111878. Epub 2020 Jan 28.
Occupational exposure to silica dust particles was the major cause of pulmonary fibrosis, and many miRNAs have been demonstrated to regulate target mRNAs in silicosis. In the present study, we found that a decreasing level of miR-411-3p in silicosis rats and lung fibroblasts induced by TGF-β1. Enlargement of miR-411-3p could inhibit the cell proliferation and migration in lung fibroblasts with TGF-β1 treatment and attenuate lung fibrosis in silicotic mice. In addition, a mechanistic study showed that miR-411-3p exert its inhibitory effect on Smad ubiquitination regulatory factor 2 (Smurf2) expression and decrease ubiquitination degradation of Smad7 regulated by smurf2, result in blocking of TGF-β/Smad signaling. We proposed that increased expression of miR-411-3p abrogates silicosis by blocking activation of TGF-β/Smad signaling through decreasing ubiquitination degradation effect of smurf2 on Smad7.
职业性暴露于二氧化硅粉尘颗粒是导致肺纤维化的主要原因，许多 miRNA 已被证明可在矽肺中调节靶 mRNAs。在本研究中，我们发现二氧化硅诱导的大鼠肺纤维化和 TGF-β1 诱导的肺成纤维细胞中 miR-411-3p 水平降低。miR-411-3p 的扩增可抑制 TGF-β1 处理后的肺成纤维细胞的增殖和迁移，并减轻矽肺小鼠的肺纤维化。此外，机制研究表明，miR-411-3p 通过抑制 Smad 泛素化调节因子 2（Smurf2）的表达和降低 Smurf2 调节的 Smad7 的泛素化降解来发挥其对 Smurf2 表达的抑制作用，从而阻断 TGF-β/Smad 信号通路。我们提出，miR-411-3p 的高表达通过降低 Smurf2 对 Smad7 的泛素化降解作用来阻断 TGF-β/Smad 信号通路的激活，从而减轻矽肺。
