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.

中文翻译：

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过度表达的microRNA-140通过下调骨糖蛋白通过Wnt信号通路抑制间质性肺疾病的肺纤维化。

间质性肺疾病（ILD）包括一组弥散性实质性肺部疾病，与大量发病率和死亡率密切相关。先前的研究强调了microRNA（miRNA）在ILD治疗中的治疗意义。因此，本研究旨在研究miR-140通过调节骨糖蛋白（OGN）-Wnt信号通路影响ILD的机制。进行基因表达微阵列分析以筛选ILD相关的差异表达基因和调控OGN的miRNA。验证了miR-140和OGN之间的靶向关系。在肺成纤维细胞中进行了异位表达和基因敲除实验，以探讨miR-140在ILD中的潜在作用机制。miR-140，OGN，通过RT-qPCR和Western blot分析确定Wnt和肺纤维化相关因子。另外，检查了细胞活力和凋亡。发现OGN受miR-140负调控。miR-140和OGN沉默的异位表达导致肺成纤维细胞凋亡和Wnt3a表达增加，以及增殖和肺纤维化减少。我们的研究结果还表明，miR-140降低了OGN，从而激活了Wnt信号通路，据观察该通路进一步影响了小鼠成纤维细胞中与肺纤维化进展相关的基因表达。总之，我们研究的关键发现表明，过表达的miR-140通过下调OGN抑制Wnt信号通路抑制ILD的发展，OGN可能被用作ILD的治疗靶标。