MDA5型
医学
皮肌炎
间质性肺病
下调和上调
病理
癌症研究
肺
内科学
生物
核糖核酸
基因
生物化学
RNA干扰
作者
Ning Shen,Xiaopeng Zhou,Xuexiao Jin,Ci Lu,Xiuhua Hu,Yichi Zhang,Yu Jiang,Qin Xu,Xiayan Xu,Minghao Liu,Linrong Lu,Yongmei Han
出处
期刊:Rheumatology
[Oxford University Press]
日期:2022-04-12
卷期号:62 (1): 373-383
被引量:10
标识
DOI:10.1093/rheumatology/keac234
摘要
This study aimed to investigate the high-resolution CT (HRCT) characteristics of anti-melanoma differentiation-associated gene 5 (MDA5) antibody positive dermatomyositis-associated interstitial lung disease (anti-MDA5 DM-ILD), and to clarify the underlying mechanisms of the clinical phenomenon.Clinical data and HRCT patterns were compared between anti-MDA5 DM-ILD (n = 32) and antisynthetase syndrome-associated ILD (ASS-ILD) (n = 29). RNA sequencing of whole-blood samples from the two groups, and in vitro experiments using human embryonic lung fibroblasts (HELFs) were conducted to explore the potential mechanisms of the clinical findings.The anti-MDA5 DM-ILD subset had a significantly higher incidence of rapidly progressive ILD (RPILD) than ASS-ILD (65.6% vs 37.9%; P = 0.031). The relative percentage of the lung fibrosis HRCT pattern was significantly lower in the anti-MDA5 DM-ILD group, especially the RPILD subgroup (P = 0.013 and 0.003, respectively). RNA sequencing detected the upregulated genes including interferon-induced helicase C domain 1 (encoding MDA5), and a trend towards downregulated expression of TGF-β signalling components in anti-MDA5 DM-ILD. In vitro culture of HELFs revealed that upregulated expression of MDA5 in HELFs was correlated with the downregulated expression of alpha smooth muscle actin, connective tissue growth factor, collagen I and collagen III by suppressing the TGF-β signalling pathway.Anti-MDA5 DM-ILD patients have significantly less lung fibrosis and elevated MDA5 expression. The upregulated expression of MDA5 has relations with the suppression of the pro-fibrotic function of fibroblasts via the TGF-β signalling pathway, which may partially explain the mechanism of the clinical phenomenon.
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