Calcitriol Suppressed Isoproterenol-induced Proliferation of Cardiac Fibroblasts via Integrin β3/FAK/Akt Pathway

被引:3
作者
Wang, Xin-feng [1 ]
Li, Qian [2 ]
Sun, Xia [1 ]
Zheng, Li-ming [3 ]
Cheng, Shao-li [3 ]
Zhu, Yan-he [4 ]
机构
[1] Xi An Jiao Tong Univ, Sch Basic Med Sci, Dept Physiol & Pathophysiol, Hlth Sci Ctr, Xian 710061, Peoples R China
[2] Xi An Jiao Tong Univ, Affiliated Hosp 2, Dept Ultrasound, Xian 710004, Peoples R China
[3] Xi An Jiao Tong Univ, Basic Med Expt Teaching Ctr, Hlth Sci Ctr, Sch Basic Med Sci, Xian 710061, Peoples R China
[4] Xi An Jiao Tong Univ, Inst Endem Dis, Hlth Sci Ctr, Sch Publ Hlth, Xian 710061, Peoples R China
基金
中国国家自然科学基金;
关键词
vitamin D; cardiac fibroblast; proliferation; integrin; myocardial fibrosis; VITAMIN-D-RECEPTOR; MEDIATED DNA-SYNTHESIS; FOCAL ADHESION KINASE; ANGIOTENSIN-II; FIBROSIS; EXPRESSION; ACTIVATION; INHIBITION; CANCER; INJURY;
D O I
10.1007/s11596-022-2681-6
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
ObjectiveCardiac 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.MethodsMTT 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 integrin beta 3.ResultsThe PCNA expression in the CFs was enhanced after isoproterenol (ISO) stimulation accompanied by an elevated expression of integrin beta-3 (beta 3). The blockade of the integrin beta 3 with a specific integrin beta 3 antibody reduced the PCNA expression induced by the ISO. Decreasing the integrin beta 3 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 integrin beta 3 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 integrin beta 3 expression in the ISO-induced myocardial injury model.ConclusionThese findings revealed a novel role for CAL in suppressing the CFs growth by the downregulation of the integrin beta 3/FAK/Akt pathway.
引用
收藏
页码:48 / 57
页数:10
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