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Mechanism of annexin a1/n-formylpeptide receptor regulation of macrophage function to inhibit hepatic stellate cell activation through Wnt/β-catenin pathway

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World Journal of Gastroenterology 2023年第22期29卷 3422-3439页

作者： Jun-Hua Fan na Luo Geng-Feng Liu Xiao-Fang Xu Shi-Quan Li Xiao-Ping Lv Department of Gastroenterology The First Affiliated Hospital of Guangxi Medical UniversityNanning 530021Guangxi Zhuang Autonomous RegionChina

BACKGROUnD Hepatic fibrosis is a common pathological process of chronic liver diseases with various causes,which can progress to *** To evaluate the effect and mechanism of action annexin(Anx)a1 in liver fibrosis and how this could be targeted *** CCl4(20%)and active n-terminal peptide of Anxa1(Ac2-26)and n-formylpeptide receptor antagonist n-Boc-Phe-Leu-Phe-Leu-Phe(Boc2)were injected intraperitoneally to induce liver fibrosis in eight wild-type mice/Anxa1 knockout mice,and to detect expression of inflammatory factors,collagen deposition,and the role of the Wnt/β-catenin pathway in hepatic *** Compared with the control group,Anxa1,transforming growth factor(TGF)-β1,interleukin(IL)-1βand IL-6 expression in the liver of mice with hepatic fibrosis induced by CCl4 was significantly increased,which promoted collagen deposition and expression ofα-smooth muscle actin(α-SMA),collagen type I and connective tissue growth factor(CTGF),and increased progressively with ***4 induced an increase in TGF-β1,IL-1βand IL-6 in liver tissue of Anxa1 knockout mice,and the degree of liver inflammation and fibrosis and expression ofα-SMA,collagen I and CTGF were significantly increased compared with in wild-type *** treatment with Ac2-26,expression of liver inflammatory factors,degree of collagen deposition and expression of a-SMA,collagen I and CTGF were decreased compared with before ***2 inhibited the anti-inflammatory and antifibrotic effects of ***1 downregulated expression of the Wnt/β-catenin pathway in CCl4-induced hepatic *** vitro,lipopolysaccharide(LPS)induced hepatocyte and hepatic stellate cell(HSC)expression of ***2-26 inhibited LPS-induced RAW264.7 cell activation and HSC proliferation,decreased expression ofα-SMA,collagen I and CTGF in HSCs,and inhibited expression of the Wnt/β-catenin pathway after HSC *** therapeutic effects were inhibited by *** Anxa1 inhibited

关键词： annexin a1 active n-terminal peptide of annexin a1 Macrophage Hepatic stellate cell Wnt/β-catenin Liver fibro

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