Silica exposure triggers inflammatory response and pulmonary fibrosis that is a severe occupational or environmental lung disease with no effective therapies. The complicated biological and molecular mechanisms underlying silica-induced lung damages have not yet been fully understood. miR-135a inhibits inflammation, apoptosis, and cancer cell proliferation. But the roles of miRNA135a involved in the silica-induced lung damages remain largely unexplored. We investigated the roles and mechanisms of miR-135a underlying silica-induced pulmonary fibrosis. The present study showed silica exposure caused the decrease in miR-135a level but the increase in inflammatory mediators. Transduction of lentivirus expressing miR-135a reduced the level of inflammatory mediators in lung tissues from silica-treated mice and improved pulmonary fibrosis which was consistent with the downregulated α-SMA but enhanced E-cadherin. Moreover, miR-135a overexpression inhibited p-p65 level in lung tissues. Overexpression of miR-135a inhibitor strengthened TLR4 protein level and NF-κB activation in BEAS-2B cells. Injection of PDTC, an inhibitor of NF-κB, further reinforced miR-135a-mediated amelioration of inflammation and pulmonary fibrosis induced by silica. The collective data indicate miR-135a restrains NF-κB activation probably through targeting TLR4 to alleviate silica-induced inflammatory response and pulmonary fibrosis.

中文翻译：

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miR-135a通过靶向NF-κB/炎性信号通路缓解二氧化硅诱导的肺纤维化。

接触二氧化硅会触发炎症反应和肺纤维化，这是一种严重的职业或环境性肺病，没有有效的治疗方法。二氧化硅引起的肺损伤的复杂生物学和分子机制尚未完全了解。miR-135a抑制炎症，凋亡和癌细胞增殖。但是，miRNA135a在二氧化硅诱导的肺损伤中所起的作用尚未得到充分探讨。我们调查了miR-135a潜在的二氧化硅诱导的肺纤维化的作用和机制。本研究表明，暴露于二氧化硅导致miR-135a水平降低，但炎症介质增加。α -SMA，但增强了E-钙黏着蛋白。此外，miR-135a过表达抑制了肺组织中的p-p65水平。的miR-135a的抑制剂的过表达增强TLR4蛋白水平和NF- κ的活化在BEAS-2B细胞。PDTC，NF-的抑制剂注入κ B，进一步增强炎症，并通过硅胶诱导的肺纤维化的的miR-135A介导的改善。集体的数据表明的miR-135a的性约束的NF- κ可能通过靶向TLR4以减轻二氧化硅诱导的炎症反应和肺纤维化的活化。