摘要：SummaryLiver 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 ofCAMSAP1also inhibited HSCs activation. This study contributes to understanding the underlying mechanism of HSCs activation and indicatesCAMSAP1may serve as a potential therapeutic target for NASH.Graphical abstractDisplay OmittedHighlights•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 activationFibrosis; Biological sciences; Immunology
