A small interfering RNA inhibits lung fibroblast-myofibroblast differentiation via simultaneously knockingdown CELF1 and activating RIG-I signalling

IF 3.7 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Biochimica et biophysica acta. Molecular cell research Pub Date : 2025-03-01 Epub Date: 2025-02-22 DOI:10.1016/j.bbamcr.2025.119924

Manman Yuan , Bingfeng Zheng , Keyi Zong , Shenglan Wang, Jing Ye, Yanjie Gao, Yang Tan, Qiang Xu, Xingxin Wu

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Abstract

Fibroblast-myofibroblast differentiation plays a key role in the pathogenesis of pulmonary fibrosis. Integrating RNA interference and RNA immunostimulation functions to treat diseases is a promising new potential therapy. Here, we report that an elevated expression of CUGBP Elav-Like Family Member 1 (CELF1), an RNA-binding protein, positively correlates with lung fibroblast-myofibroblast differentiation in fibrotic lung tissues. Knockdown of CELF1 expression by siRNA-17834 or siRNA-116447 inhibited lung fibroblast-myofibroblast differentiation via promoting the anti-fibrotic IL7 mRNA stability. Interestingly, siRNA-17834 but not siRNA-116447 unexpectedly induced Retinoic Acid-inducible Gene I (RIG-I) dependent IFN-β production, which also inhibited lung fibroblast-myofibroblast differentiation. In conclusion, siRNA-17834 has dual functions of RNA interference and RNA immunostimulation to control lung fibroblast-myofibroblast differentiation, which suggests a novel strategy for the treatment of pulmonary fibrosis.

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一种小干扰RNA通过同时敲除CELF1和激活rig - 1信号抑制肺成纤维细胞向肌成纤维细胞分化。

成纤维细胞-肌成纤维细胞分化在肺纤维化的发病机制中起关键作用。结合RNA干扰和RNA免疫刺激功能治疗疾病是一种很有前景的新疗法。在这里，我们报道了CUGBP elaf - like Family Member 1 （CELF1）的表达升高，这是一种rna结合蛋白，与纤维化肺组织中肺成纤维细胞-肌成纤维细胞分化呈正相关。通过siRNA-17834或siRNA-116447敲低CELF1表达，通过促进抗纤维化IL7 mRNA的稳定性，抑制肺成纤维细胞-肌成纤维细胞分化。有趣的是，siRNA-17834而非siRNA-116447意外诱导视黄酸诱导基因I （RIG-I）依赖的IFN-β产生，这也抑制肺成纤维细胞-肌成纤维细胞分化。综上所述，siRNA-17834具有RNA干扰和RNA免疫刺激的双重功能，控制肺成纤维细胞-肌成纤维细胞分化，为肺纤维化的治疗提供了一种新的策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biochimica et biophysica acta. Molecular cell research 生物-生化与分子生物学

CiteScore

10.00

自引率

2.00%

发文量

151

审稿时长

44 days

期刊介绍： BBA Molecular Cell Research focuses on understanding the mechanisms of cellular processes at the molecular level. These include aspects of cellular signaling, signal transduction, cell cycle, apoptosis, intracellular trafficking, secretory and endocytic pathways, biogenesis of cell organelles, cytoskeletal structures, cellular interactions, cell/tissue differentiation and cellular enzymology. Also included are studies at the interface between Cell Biology and Biophysics which apply for example novel imaging methods for characterizing cellular processes.