Department of Rheumatology, The Second Affiliated Hospital of Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou 310009, China; Department of Clinic Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou 310009, China.
Department of Rheumatology, The Second Affiliated Hospital of Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou 310009, China.
Genomics. 2022 Jul;114(4):110391. doi: 10.1016/j.ygeno.2022.110391. Epub 2022 May 26.
To investigate the role and mechanism of microRNAs (miRNAs) in fibrotic processes involved in the pathology of systemic sclerosis (SSc).
R language and bioinformatics methods were used to identify differential miRNAs and mRNAs and analyze their biological functions. Transfection experiments were performed to evaluate the function and regulatory mechanism of miR-27a-3p in vitro. Levels of fibrosis-related genes, SPP1 and cell proliferation were assessed.
MiR-27a-3p is reduced both in SSc lung and skin tissues. Overexpression of miR-27a-3p significantly inhibited fibrosis-related genes expression and protein abundance and cell proliferation, whereas inhibition of miR-27a-3p significantly enhanced these phenomena. Moreover, miR-27a-3p exerts its anti-fibrosis effect by negatively regulating SPP1 and ERK signal, more prominent in fibroblasts.
Our findings show that miR-27a-3p regulates a common mechanism in the process of SSc skin and lung fibrosis. MiR-27a-3p/SPP1/ERK1/2 axis may be an important target for delaying the progression of SSc fibrosis.
探讨 microRNAs（miRNAs）在系统性硬化症（SSc）病理纤维化过程中的作用及机制。
采用 R 语言和生物信息学方法鉴定差异表达的 miRNAs 和 mRNAs，并分析其生物学功能。体外转染实验评估 miR-27a-3p 的功能及其调控机制。检测纤维化相关基因 SPP1 及细胞增殖水平。
miR-27a-3p 在 SSc 肺组织和皮肤组织中均下调。miR-27a-3p 过表达可显著抑制纤维化相关基因表达和蛋白丰度及细胞增殖，而抑制 miR-27a-3p 则显著增强这些现象。此外，miR-27a-3p 通过负调控 SPP1 和 ERK 信号通路发挥抗纤维化作用，在成纤维细胞中更为明显。
我们的研究结果表明，miR-27a-3p 调节 SSc 皮肤和肺纤维化过程中的共同机制。miR-27a-3p/SPP1/ERK1/2 轴可能是延缓 SSc 纤维化进展的重要靶点。
