M2 macrophage-derived exosomal microRNA-411-5p impedes the activation of hepatic stellate cells by targeting CAMSAP1 in NASH model.
M2 macrophage-derived exosomal microRNA-411-5p impedes the activation of hepatic stellate cells by targeting CAMSAP1 in NASH model.
复制标题
NASH 模型中 M2 巨噬细胞来源的外泌体 microRNA-411-5p 通过靶向 CAMSAP1 阻碍肝星状细胞的激活
DOI：
10.1016/j.isci.2022.104597
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发表时间：
2022-07-15
期刊：
影响因子：
5.8
通讯作者：
Deng, Hong
中科院分区：
文献类型：
--
作者：
Wan, Zhiping;Yang, Xiaoan;Liu, Xiaoquan;Sun, Yinfang;Yu, Piaojian;Xu, Fen;Deng, Hong
肝纤维化是非酒精性脂肪性肝病（NAFLD）的一个严重阶段，与肝星状细胞（hsc）的活化及其与巨噬细胞的相互作用密切相关。外泌体可以介导nafld相关纤维化中巨噬细胞和hsc之间的串扰。我们发现M2巨噬细胞来源的外泌体显著抑制hsc的激活。RNA-seq研究显示，与健康对照组相比，非酒精性脂肪性肝炎（NASH）患者血清外泌体中的miRNA-411-5p降低。此外，NASH模型肝脏中miR-411-5p和M2巨噬细胞标志物降低。我们进一步证明M2巨噬细胞外泌体miR-411-5p抑制hsc活化，miR-411-5p直接下调Calmodulin-Regulated Spectrin-Associated Protein 1 （CAMSAP1）的表达，使星状细胞失活。重要的是，CAMSAP1的敲低也抑制了hsc的激活。这项研究有助于理解造血干细胞活化的潜在机制，并表明CAMSAP1可能作为NASH的潜在治疗靶点。在hfhcd诱导的NASH大鼠模型中，M2巨噬细胞标志物降低，M2巨噬细胞衍生的外泌体通过miR-411-5p抑制hsc的激活CAMSAP1是miR-411-5p的直接靶点，CAMSAP1的敲低抑制hsc的激活纤维化；生物科学;免疫学
Liver fibrosis is a severe stage of nonalcoholic fatty liver disease (NAFLD), which is closely associated with the activation of hepatic stellate cells (HSCs) and their interaction with macrophages. Exosomes can mediate crosstalk between macrophages and HSCs in NAFLD-associated fibrosis. We found that M2 macrophage-derived exosomes significantly inhibit HSCs activation. RNA-seq studies revealed that miRNA-411-5p was decreased in serum exosomes of nonalcoholic steatohepatitis (NASH) patients as compared with that in healthy controls. Besides, miR-411-5p and M2 macrophage markers are decreased in the liver of the NASH model. We further proved that exosomal miR-411-5p from M2 macrophages inhibit HSCs activation and miR-411-5p directly downregulated the expression of Calmodulin-Regulated Spectrin-Associated Protein 1 (CAMSAP1) to inactivate stellate cells. Importantly, knockdown of CAMSAP1 also inhibited HSCs activation. This study contributes to understanding the underlying mechanism of HSCs activation and indicates CAMSAP1 may serve as a potential therapeutic target for NASH. M2 macrophage markers are decreased in the HFHCD-induced rat model of NASH M2 macrophage-derived exosomes inhibit HSCs activation via miR-411-5p CAMSAP1 is a direct target of miR-411-5p Knockdown of CAMSAP1 inhibits HSCs activation Fibrosis; Biological sciences; Immunology
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影响因子：
16
作者：
Lötvall J;Hill AF;Hochberg F;Buzás EI;Di Vizio D;Gardiner C;Gho YS;Kurochkin IV;Mathivanan S;Quesenberry P;Sahoo S;Tahara H;Wauben MH;Witwer KW;Théry C
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影响因子：
29.4
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影响因子：
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作者：
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影响因子：
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