{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T13:51:49Z","timestamp":1782481909615,"version":"3.54.5"},"reference-count":31,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T00:00:00Z","timestamp":1778198400000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001411","name":"Indian Council of Medical Research","doi-asserted-by":"publisher","award":["5\/4\/1\u20101\/2020\u2010NCD\u20101 (2020\u20103775)"],"award-info":[{"award-number":["5\/4\/1\u20101\/2020\u2010NCD\u20101 (2020\u20103775)"]}],"id":[{"id":"10.13039\/501100001411","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["iubmb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BioFactors"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Angiotensin II (Ang II), a potent profibrotic stimulus, exhibits pleiotropic effects on cardiac cells. The fate of c\u2010Kit\n                    <jats:sup>+<\/jats:sup>\n                    cells in an Ang II\u2010elevated injured myocardium remains poorly defined. This study investigated, in\u00a0vitro, the effect of Ang II on the phenotype of non\u2010hematopoietic non\u2010endothelial c\u2010Kit\n                    <jats:sup>+<\/jats:sup>\n                    cardiac interstitial cells (CICs), expressing OCT4. Our findings demonstrate that Ang II directly drives the phenotypic transition of c\u2010Kit\n                    <jats:sup>+<\/jats:sup>\n                    CICs into \u03b1\u2010SMA\u2010expressing myofibroblasts, accompanied by significant upregulation of prominent myofibroblast markers, SM22\u2010\u03b1, collagen type IA, and its crosslinking enzyme, lysyl oxidase. Through targeted silencing experiments, we confirmed that Ang II\u2010mediated phenotypic transition occurs via activation of the ERK1\/2 MAPK pathway, triggered by collagen receptor Discoidin domain receptor 2 (DDR2), and involves the transcription factor, serum response factor (SRF). These results indicate that c\u2010Kit\n                    <jats:sup>+<\/jats:sup>\n                    CICs are susceptible to myofibroblast transition in the infarcted myocardium, and may serve as an additional source of myofibroblasts contributing to repair and remodeling alongside resident fibroblasts. Additionally, we observed that overexpression of c\u2010Kit attenuated Ang II\u2010induced \u03b1\u2010SMA upregulation by downregulating DDR2\u2010ERK1\/2\u2010SRF signaling in c\u2010Kit\n                    <jats:sup>+<\/jats:sup>\n                    CICs, highlighting the pivotal role of c\u2010Kit expression levels in regulating cell fate. Furthermore, overexpression of c\u2010Kit in Ang II\u2010treated cardiac fibroblasts significantly reduced the expression of myofibroblast proteins, \u03b1\u2010SMA, SM22\u2010\u03b1, periostin, collagen type IA, collagen receptor DDR2, and lysyl oxidase, and resembled c\u2010Kit\n                    <jats:sup>+<\/jats:sup>\n                    CICs in morphology. Collectively, these results suggest that c\u2010Kit expression in myofibroblasts may potentially mitigate the adverse effects of cardiac fibrosis and promote favorable remodeling in the long term.\n                  <\/jats:p>","DOI":"10.1002\/biof.70108","type":"journal-article","created":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T04:32:32Z","timestamp":1778301152000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Angiotensin\n                    <scp>II<\/scp>\n                    Promotes the Phenotypic Transition of c\u2010Kit\n                    <sup>+<\/sup>\n                    Cardiac Interstitial Cells to Myofibroblasts Through Collagen Receptor Discoidin Domain Receptor 2"],"prefix":"10.1002","volume":"52","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-2223-5847","authenticated-orcid":false,"given":"Indraja","family":"Devidasan","sequence":"first","affiliation":[{"name":"Division of Cellular and Molecular Cardiology, Department of Pathology Sree Chitra Tirunal Institute for Medical Sciences and Technology  Trivandrum India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9766-9888","authenticated-orcid":false,"given":"Sruthi","family":"Radhakrishnan","sequence":"additional","affiliation":[{"name":"Division of Cellular and Molecular Cardiology, Department of Pathology Sree Chitra Tirunal Institute for Medical Sciences and Technology  Trivandrum India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5325-2150","authenticated-orcid":false,"given":"Sarayu","family":"Gopal","sequence":"additional","affiliation":[{"name":"Division of Cellular and Molecular Cardiology, Department of Pathology Sree Chitra Tirunal Institute for Medical Sciences and Technology  Trivandrum 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Technology  Trivandrum India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4595-2331","authenticated-orcid":false,"given":"Neethu","family":"Mohan","sequence":"additional","affiliation":[{"name":"Division of Cellular and Molecular Cardiology, Department of Pathology Sree Chitra Tirunal Institute for Medical Sciences and Technology  Trivandrum 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