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Calcitonin gene-related peptide inhibits the cardiac fibroblasts senescence in cardiac fibrosis via up-regulating klotho expression

It has been documented cardiac fibroblasts as the predominant cell population undergoing senescence in heart. Calcitonin gene-related peptide (CGRP) exhibits a wide range of cardiovascular protective effects. Whether CGRP protects against cardiac fibroblasts senescence in cardiac fibrosis remains un...

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Published in:European journal of pharmacology 2019-01, Vol.843, p.96-103
Main Authors: Li, Wen-Qun, Tan, Sheng-Lan, Li, Xiao-Hui, Sun, Tao-Li, Li, Dai, Du, Jie, Wei, Shan-Shan, Li, Yuan-Jian, Zhang, Bi-Kui
Format: Article
Language:English
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Summary:It has been documented cardiac fibroblasts as the predominant cell population undergoing senescence in heart. Calcitonin gene-related peptide (CGRP) exhibits a wide range of cardiovascular protective effects. Whether CGRP protects against cardiac fibroblasts senescence in cardiac fibrosis remains unknown. Here, we detected the down-regulation of CGRP concomitant with senescence in fibrotic myocardium, both hypertension- induced left ventricular fibrosis in SHR rats and hypoxia-induced right ventricular fibrosis in pulmonary artery hypertension rats. Exogenous CGRP inhibited the cardiac fibroblasts senescence and senescence-associated secretory phenotype (SASP) induced by TGF-β1, which was abolished by CGRP8–37, a selective CGRP receptor antagonist. Moreover, the expression of klotho, an anti-senescence protein, was down-regulated in fibrotic myocardium, and CGRP up-regulated the klotho expression in TGF-β1-treated cardiac fibroblasts. Klotho knockdown by siRNA reversed the inhibition of CGRP on senescence and SASP induced by TGF-β1 in cardiac fibroblasts. These results suggested that CGRP inhibited the cardiac fibroblasts senescence and SASP in cardiac fibrosis via up-regulating klotho expression. [Display omitted]
ISSN:0014-2999
1879-0712
DOI:10.1016/j.ejphar.2018.10.023