Macrophage polarization is involved in liver fibrosis induced byβ_(1)-adrenoceptor autoantibody

查看全文 作　　者：Ye [1,2]Wu;Xiongxiong [1,2]Fan;Haicun [3]Yu;Jingyi [4]Liu;Yanru [1,2]Duan;Suli [1,2]Zhang;Li [5]Yan;Yunhui [6]Du;Huirong [1,2]Liu

机构地区：[1]Department of Physiology and Pathophysiology,School of Basic Medical Sciences,Capital Medical University,Beijing 100069,China;[2]Beijing key laboratory of metabolic disorder related cardiovascular disease,School of Basic Medical Sciences,Capital Medical University,Beijing 100069,China;[3]Zhengzhou Central Hospital affiliated of Zhengzhou University,Zhengzhou 450000,China;[4]Shanxi Cardiovascular Hospital,Cardiac Care Unit,Taiyuan 030024,China;[5]Department of Pathophysiology,Institute of Basic Medical Science,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100005,China;[6]Beijing Anzhen Hospital,Capital Medical University,Beijing Institute of Heart,Lung and Blood Vessel Diseases,Beijing100029,China

出　　处：《Acta Biochimica et Biophysica Sinica》索引2022年第54卷第8期,共13页

基　　金：the grants from the National Natural Science Foundation of China(Nos.81970334 and 81770393 to H.L.)。 摘　　要：Accumulating evidence suggests that liver injury can be induced by the over-expression ofβ_(1)-adrenergic receptors(β_(1)-ARs).High titers of autoantibodies specific toβ_(1)-adrenergic receptors(β_(1)-AA)are detected in the sera of heart failure patients,potentially playing agonist-like roles.However,the role ofβ_(1)-AA in liver function has not been characterized.In this study,we collect the sera of primary biliary cholangitis(PBC)patients,a condition which easily develops into liver fibrosis,and analyze the relationship between PBC andβ_(1)-AA.A passive immunization model is established to assess the effect ofβ_(1)-AA on the liver.Subsequently,the effect ofβ_(1)-AA on macrophages is investigated in vitro.Results show that PBC patients have a high titer and ratio ofβ_(1)-AA,compared to controls.Liver injury and fibrosis are induced byβ_(1)-AA.In vitro experiments with ROS probe demonstrate thatβ_(1)-AA induces macrophages to produce ROS and secrete TNFα.These effects can be partially reversed by metoprolol,a blocker forβ_(1)-AR.Results from the transwell and phagocytosis assays show thatβ_(1)-AA promotes macrophage migration and phagocytosis.FCM tests suggest thatβ_(1)-AA induces the alteration of M1 rather than M2 markers in macrophages.Finally,the Annexin V/PI assay indicates that macrophage culture supernatants stimulated byβ_(1)-AA cause hepatocyte apoptosis.Overall,these results suggest thatβ_(1)-AA is involved in PBC.Theβ_(1)-AA-induced activation,phagocytosis and phenotypic modification of macrophages may play an important role in the development of hepatic fibrosis and injury. 关键词：β_(1)-adrenergic receptor AUTOANTIBODY hepatic fibrosis MACROPHAGES

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Macrophage polarization is involved in liver fibrosis induced byβ_(1)-adrenoceptor autoantibody

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