Department of Chest Surgery, Linyi People's Hospital, Linyi, People's Republic of China.
Operation Room, Linyi People's Hospital, Linyi, People's Republic of China.
Am J Physiol Cell Physiol. 2020 Nov 1;319(5):C895-C905. doi: 10.1152/ajpcell.00479.2019. Epub 2020 Aug 5.
Interstitial lung disease (ILD) comprises of a group of diffuse parenchymal lung disorders that are strongly associated with substantial morbidity and mortality. Previous studies have highlighted the therapeutic significance of microRNAs (miRNAs) in the treatment of ILD. Thus this study aims to investigate the mechanism by which miR-140 affects ILD through the regulation of osteoglycin (OGN)Wnt signaling pathway. Gene expression microarray analysis was performed to screen ILD-related differentially expressed genes and miRNAs that regulated OGN. The targeting relationship between miR-140 and OGN was verified. Ectopic expression and knockdown experiments were performed in lung fibroblasts to explore the potential mechanism of action of miR-140 in ILD. The expression of miR-140, OGN, as well as Wnt- and pulmonary fibrosis-related factors, was determined by RT-qPCR and Western blot analysis. In addition, cell viability and apoptosis were examined. OGN was found to be negatively regulated by miR-140. The ectopic expression of miR-140 and OGN silencing resulted in increased lung fibroblast apoptosis and Wnt3a expression, along with reduced proliferation and pulmonary fibrosis. Our results also revealed that miR-140 decreased OGN, thereby activating the Wnt signaling pathway, which was observed to further affect the expression of genes associated with the progression of pulmonary fibrosis in mouse fibroblasts. In conclusion, the key findings from our study suggest that overexpressed miR-140 suppresses ILD development via the Wnt signaling pathway by downregulating OGN, which could potentially be used as a therapeutic target for ILD.
间质性肺病（ILD）包括一组弥漫性实质肺疾病，与高发病率和死亡率密切相关。先前的研究强调了 microRNAs（miRNAs）在治疗ILD 中的治疗意义。因此，本研究旨在通过调节骨桥蛋白（OGN）Wnt 信号通路来研究 miR-140 影响 ILD 的机制。进行基因表达微阵列分析以筛选与 ILD 相关的差异表达基因和调节 OGN 的 miRNAs。验证了 miR-140 与 OGN 之间的靶向关系。在肺成纤维细胞中进行异位表达和敲低实验，以探索 miR-140 在 ILD 中的潜在作用机制。通过 RT-qPCR 和 Western blot 分析测定 miR-140、OGN 以及 Wnt 和肺纤维化相关因子的表达。此外，还检查了细胞活力和细胞凋亡。发现 OGN 受 miR-140 负调控。miR-140 的异位表达和 OGN 沉默导致肺成纤维细胞凋亡和 Wnt3a 表达增加，同时增殖和肺纤维化减少。我们的结果还表明，miR-140 降低了 OGN，从而激活了 Wnt 信号通路，这进一步观察到它影响了与小鼠成纤维细胞中肺纤维化进展相关的基因的表达。总之，我们研究的主要发现表明，过表达的 miR-140 通过下调 OGN 抑制 Wnt 信号通路，从而可能成为 ILD 的治疗靶点。
