Calcitriol Suppressed Isoproterenol-induced Proliferation of Cardiac Fibroblasts via Integrinβ3/FAK/Akt Pathway  

作　　者：Xin-feng WANG Qian LI Xia SUN Li-ming ZHENG Shao-li CHENG Yan-he ZHU 

机构地区：[1]Department of Physiology and Pathophysiology,School of Basic Medical Sciences,Xi’an Jiaotong University Health Science Center,Xi’an,710061,China [2]Department of Ultrasound,the Second Affiliated Hospital of Xi’an Jiaotong University,Xi’an,710004,China [3]Basic Medical Experimental Teaching Center,School of Basic Medical Sciences,Xi’an Jiaotong University Health Science Center,Xi’an,710061,China [4]Institute of Endemic Diseases,School of Public Health,Xi’an Jiaotong University Health Science Center,Xi’an,710061,China

出　　处：《Current Medical Science》2023年第1期48-57,共10页当代医学科学（英文）

基　　金：supported by grants from the National Natural Science Foundation of China(No.81441016)and Key R&D Plan in Shaanxi Province of China(No.2020SF-262 and No.2019SF-200).

摘　　要：Objective Cardiac fibroblasts(CFs)proliferation and extracellular matrix deposition are important features of cardiac fibrosis.Various studies have indicated that vitamin D displays an anti-fibrotic property in chronic heart diseases.This study explored the role of vitamin D in the growth of CFs via an integrin signaling pathway.Methods MTT and 5-ethynyl-2′-deoxyuridine assays were performed to determine cell viability.Western blotting was performed to detect the expression of proliferating cell nuclear antigen(PCNA)and integrin signaling pathway.The fibronectin was observed by ELISA.Immunohistochemical staining was employed to evaluate the expression of integrinβ3.Results The PCNA expression in the CFs was enhanced after isoproterenol(ISO)stimulation accompanied by an elevated expression of integrin beta-3(β3).The blockade of the integrinβ3 with a specific integrinβ3 antibody reduced the PCNA expression induced by the ISO.Decreasing the integrinβ3 by siRNA reduced the ISO-triggered phosphorylation of FAK and Akt.Both the FAK inhibitor and Akt inhibitor suppressed the PCNA expression induced by the ISO in the CFs.Calcitriol(CAL),an active form of vitamin D,attenuated the ISO-induced CFs proliferation by downregulating the integrinβ3 expression,and phosphorylation of FAK and Akt.Moreover,CAL reduced the increased levels of fibronectin and hydroxyproline in the CFs culture medium triggered by the ISO.The administration of calcitriol decreased the integrinβ3 expression in the ISO-induced myocardial injury model.Conclusion These findings revealed a novel role for CAL in suppressing the CFs growth by the downregulation of the integrinβ3/FAK/Akt pathway.

关 键 词：vitamin D cardiac fibroblast PROLIFERATION INTEGRIN myocardial fibrosis 

分 类 号：R541[医药卫生—心血管疾病]