{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T05:38:45Z","timestamp":1761197925349,"version":"build-2065373602"},"reference-count":44,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,3,13]],"date-time":"2021-03-13T00:00:00Z","timestamp":1615593600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["HL131546, HL149696, HL122906, T32HL007260, F31HL152494, F31HL142159"],"award-info":[{"award-number":["HL131546, HL149696, HL122906, T32HL007260, F31HL152494, F31HL142159"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["TPA34850095, SRG35540029, TPA34900016, CSA33590067, PRE34080172"],"award-info":[{"award-number":["TPA34850095, SRG35540029, TPA34900016, CSA33590067, PRE34080172"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006955","name":"Office of Extramural Research, National Institutes of Health","doi-asserted-by":"publisher","award":["C06RR018823"],"award-info":[{"award-number":["C06RR018823"]}],"id":[{"id":"10.13039\/100006955","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["GM103444, GM132055"],"award-info":[{"award-number":["GM103444, GM132055"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCDD"],"abstract":"<jats:p>Mitral valve prolapse (MVP) is a common form of valve disease and can lead to serious secondary complications. The recent identification of MVP causal mutations in primary cilia-related genes has prompted the investigation of cilia-mediated mechanisms of disease inception. Here, we investigate the role of platelet-derived growth factor receptor-alpha (PDGFR\u03b1), a receptor known to be present on the primary cilium, during valve development using genetically modified mice, biochemical assays, and high-resolution microscopy. While PDGFR\u03b1 is expressed throughout the ciliated valve interstitium early in development, its expression becomes restricted on the valve endocardium by birth and through adulthood. Conditional ablation of Pdgfra with Nfatc1-enhancer Cre led to significantly enlarged and hypercellular anterior leaflets with disrupted endothelial adhesions, activated ERK1\/2, and a dysregulated extracellular matrix. In vitro culture experiments confirmed a role in suppressing ERK1\/2 activation while promoting AKT phosphorylation. These data suggest that PDGFR\u03b1 functions to suppress mesenchymal transformation and disease phenotypes by stabilizing the valve endocardium through an AKT\/ERK pathway.<\/jats:p>","DOI":"10.3390\/jcdd8030028","type":"journal-article","created":{"date-parts":[[2021,3,14]],"date-time":"2021-03-14T22:13:10Z","timestamp":1615759990000},"page":"28","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["PDGFR\u03b1: Expression and Function during Mitral Valve Morphogenesis"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3214-7010","authenticated-orcid":false,"given":"Kelsey","family":"Moore","sequence":"first","affiliation":[{"name":"Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Suite 601 Basic Science Building, 173 Ashley Avenue, Charleston, SC 29425, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diana","family":"Fulmer","sequence":"additional","affiliation":[{"name":"Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Suite 601 Basic Science Building, 173 Ashley Avenue, Charleston, SC 29425, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9376-3274","authenticated-orcid":false,"given":"Lilong","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Suite 601 Basic Science Building, 173 Ashley Avenue, Charleston, SC 29425, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalie","family":"Koren","sequence":"additional","affiliation":[{"name":"Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Suite 601 Basic Science Building, 173 Ashley Avenue, Charleston, SC 29425, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janiece","family":"Glover","sequence":"additional","affiliation":[{"name":"Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Suite 601 Basic Science Building, 173 Ashley Avenue, Charleston, SC 29425, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reece","family":"Moore","sequence":"additional","affiliation":[{"name":"Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Suite 601 Basic Science Building, 173 Ashley Avenue, Charleston, SC 29425, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8492-3536","authenticated-orcid":false,"given":"Cortney","family":"Gensemer","sequence":"additional","affiliation":[{"name":"Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Suite 601 Basic Science Building, 173 Ashley Avenue, Charleston, SC 29425, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1717-8943","authenticated-orcid":false,"given":"Tyler","family":"Beck","sequence":"additional","affiliation":[{"name":"Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Suite 601 Basic Science Building, 173 Ashley Avenue, Charleston, SC 29425, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2168-9671","authenticated-orcid":false,"given":"Jordan","family":"Morningstar","sequence":"additional","affiliation":[{"name":"Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Suite 601 Basic Science Building, 173 Ashley Avenue, Charleston, SC 29425, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1760-2767","authenticated-orcid":false,"given":"Rebecca","family":"Stairley","sequence":"additional","affiliation":[{"name":"Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Suite 601 Basic Science Building, 173 Ashley Avenue, Charleston, SC 29425, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Russell A.","family":"Norris","sequence":"additional","affiliation":[{"name":"Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Suite 601 Basic Science Building, 173 Ashley Avenue, Charleston, SC 29425, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,13]]},"reference":[{"key":"ref_1","first-page":"91","article-title":"Valvular heart disease: The next cardiac 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