LncRNA gm40262 promotes liver fibrosis and parasite growth through the gm40262-miR-193b-5p-TLR4/Col1α1 axis

文献类型： 外文期刊

第一作者： Liu, Tingli

作者： Liu, Tingli;Pu, Guiting;Wang, Liqun;Li, Hong;Li, Yanping;Guo, Xiaola;Yin, Hong;Luo, Xuenong;Liu, Tingli;Ye, Ziyu;Li, Rui;Zheng, Yadong;Cho, William C.;Yin, Hong;Luo, Xuenong

作者机构：

关键词： E. multilocularis; liver fibrosis; gm40262; miR-193b-5p; TLR4; Col1 alpha 1

期刊名称：MBIO （ 影响因子：4.7； 五年影响因子：5.5 ）

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年卷期： 2025 年 16 卷 4 期

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收录情况： SCI

摘要： Alveolar echinococcosis (AE) is a severe and life-threatening parasitic disease caused by Echinococcus multilocularis. Liver fibrosis is a significant pathological feature of advanced AE, characterized by the excessive production and accumulation of extracellular matrix (ECM). However, the precise underlying mechanism remains largely unknown. In this study, we show that the long noncoding RNA gm40262, predominantly expressed in hepatic stellate cells (HSCs), is upregulated in AE. Interestingly, its knock down leads to liver fibrosis resolution, accompanied by a substantial suppression of parasite growth. Gm40262 functions by targeting miR-193b-5p to activate HSCs and stimulate their proliferation in a TGF-beta-dependent manner, thereby promoting ECM production by upregulating Col1 alpha 1. Moreover, gm40262 is also involved in inflammation through the gm40262-miR-193b-5p-TLR4 axis. Our findings suggest that gm40262 plays a pivotal role in parasite-induced liver fibrosis through multiple mechanisms, highlight ing its potential as a therapeutic target for hepatic fibrosis.

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