{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T10:43:16Z","timestamp":1787740996584,"version":"build-2784847793"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2019,8,28]],"date-time":"2019-08-28T00:00:00Z","timestamp":1566950400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81703518"],"award-info":[{"award-number":["81703518"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81573486"],"award-info":[{"award-number":["81573486"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["91639114"],"award-info":[{"award-number":["91639114"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81773734"],"award-info":[{"award-number":["81773734"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81703592"],"award-info":[{"award-number":["81703592"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Hunan Provincial Natural Scientific Foundation","award":["2019JJ50849"],"award-info":[{"award-number":["2019JJ50849"]}]},{"name":"Scientific Research Project of Hunan Provincial Health and Family Planning Commission","award":["B20180253"],"award-info":[{"award-number":["B20180253"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>Aberrant activation of cardiac fibroblasts leads to cardiac fibrosis, and evolving evidences suggest that endogenous bioactive substances derived from cardiac fibroblasts regulate cardiac fibroblasts activation in an autocrine\/paracrine manner. Here we first presented evidence that cardiac fibroblasts can synthesize and secrete calcitonin gene-related peptide (CGRP), therefore, this study aimed to investigate the role of cardiac fibroblasts-derived CGRP in cardiac fibroblasts activation and its regulative mechanism.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>The abundantly expression of CGRP in rat, mouse, and human myocardium allowed us to explore the cellular origin of CGRP, and found that the cardiac CGRP was mainly derived from cardiac fibroblasts. Activating TRPA1 with a specific agonist allyl isothiocyanate promoted the synthesis and secretion of CGRP, as well as intracellular Ca2+. These effects were reversed by TRPA1-specific antagonist HC030031 and Ca2+ chelator BAPTA-AM. TGF-\u03b21 was applied to induce the activation of cardiac fibroblasts, and found that TGF-\u03b21 can increase the mRNA expression and secretion levels of CGRP in cardiac fibroblasts. Either CGRP8\u201337 (CGRP receptor antagonist) or \u03b1-CGRP small interfering RNA (siRNA) aggravated TGF-\u03b21-induced proliferation, differentiation, collagen production, and instigated inflammation in cardiac fibroblasts. Moreover, TGF-\u03b21-induced NF-\u03baB activation including I\u03baB\u03b1 phosphorylation and p65 nuclear translocation were also promoted by CGRP8\u201337 and \u03b1-CGRP siRNA. NF-\u03baB inhibitor pyrrolidinedithiocarbamate ammonium (PDTC) reversed the effects of CGRP8\u201337 on NF-\u03baB activation. The promotive effects of CGRP8\u201337 on TGF-\u03b21-induced activation of cardiac fibroblasts were all reversed by PDTC. Monocrotaline (MCT) induces pulmonary arterial hypertension, progressively leading to right ventricular fibrosis. This model of cardiac fibrosis was developed here to test the potentially beneficial effects of TRPA1 activation in vivo. The non-toxic TRPA1 agonist Cinnamaldehyde (CA) inhibited MCT-induced elevation in right ventricle systolic pressure, RV\/LV\u2009+\u2009S, and right ventricular collagen accumulation, as well as down-regulation of CGRP. CA increased the synthesis and secretion of CGRP, and inhibited TGF-\u03b21-induced activation in cardiac fibroblasts.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Our data suggested an autocrine role for cardiac fibroblasts-derived CGRP in suppressing activation of cardiac fibroblasts through inhibiting NF-\u03baB activation. Increasing autocrine CGRP by activating TRPA1 can ameliorate cardiac fibrosis. These findings support the notion that CGRP derived from cardiac fibroblasts is an endogenous suppressor of cardiac fibrosis.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cvr\/cvz234","type":"journal-article","created":{"date-parts":[[2019,8,26]],"date-time":"2019-08-26T11:38:17Z","timestamp":1566819497000},"page":"1335-1348","source":"Crossref","is-referenced-by-count":42,"title":["CGRP derived from cardiac fibroblasts is an endogenous suppressor of cardiac fibrosis"],"prefix":"10.1093","volume":"116","author":[{"given":"Wenqun","family":"Li","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Xiangya School of Pharmaceutical Sciences, Central South University, No. 172 Tongzipo Road, Changsha, Hunan 410078, China"},{"name":"Department of Pharmacy, The Second Xiangya Hospital, Central South University, No. 139 Renmin Middle Road, Changsha, Hunan 410011, 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