文章基本信息

标题：SAA1/TLR2 axis directs chemotactic migration of hepatic stellate cells responding to injury
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作者：Anteneh Getachew ; Nasir Abbas ; Kai You 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2021
卷号：24
期号：5
页码：1-25
DOI：10.1016/j.isci.2021.102483
语种：English
出版社：Elsevier
摘要：SummaryHepatic stellate cells (HSCs) are crucial for liver injury repair and cirrhosis. However, the mechanism of chemotactic recruitment of HSCs into injury loci is still largely unknown. Here, we demonstrate that serum amyloid A1 (SAA1) acts as a chemokine recruiting HSCs toward injury loci signaling via TLR2, a finding proven by gene manipulation studies in cell and mice models. The mechanistic investigations revealed that SAA1/TLR2 axis stimulates the Rac GTPases through PI3K-dependent pathways and induces phosphorylation of MLC (pSer19). Genetic deletion of TLR2 and pharmacological inhibition of PI3K diminished the phosphorylation of MLCpSer19 and migration of HSCs. In brief, SAA1 serves as a hepatic endogenous chemokine for the TLR2 receptor on HSCs, thereby initiating PI3K-dependent signaling and its effector, Rac GTPases, which consequently regulates actin filament remodeling and cell directional migration. Our findings provide novel targets for anti-fibrosis drug development.Graphical abstractDisplay OmittedHighlights•SAA1 serves as a chemokine to guide migration of HSCs toward injury locus•TLR2 acts as a functional receptor for SAA1 in HSCs•SAA1/TLR2 axis-mediated migration of HSCs operates through PI3K/Rac1 signaling•SAA1/TLR2 axis provides a link for the cross talk between hepatocytes and HSCsBiochemistry; Cell engineering; Cell biology