{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T20:19:04Z","timestamp":1784233144804,"version":"3.55.0"},"reference-count":51,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2022,6,17]],"date-time":"2022-06-17T00:00:00Z","timestamp":1655424000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003449","name":"Green Lane Research and Educational Fund","doi-asserted-by":"publisher","award":["19\/43\/4145"],"award-info":[{"award-number":["19\/43\/4145"]}],"id":[{"id":"10.13039\/501100003449","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Heart valve disease is a growing problem worldwide. Though very common in older adults, the mechanisms behind the development of the disease aren\u2019t well understood, and at present the only therapeutic option is valve replacement. Valvular interstitial cells (VICs) may hold the answer. These cells can undergo pathological differentiation into contractile myofibroblasts or osteoblasts, leading to thickening and calcification of the valve tissue. Our study aimed to characterise the effect of fibroblast growth factor 2 (FGF-2) on the differentiation potential of VICs. We isolated VICs from diseased human valves and treated these cells with FGF-2 and TGF-\u03b2 to elucidate effect of these growth factors on several myofibroblastic outcomes, in particular immunocytochemistry and gene expression. We used TGF-\u03b2 as a positive control for myofibroblastic differentiation. We found that FGF-2 promotes a \u2018quiescent-type\u2019 morphology and inhibits the formation of \u03b1-smooth muscle actin positive myofibroblasts. FGF-2 reduced the calcification potential of VICs, with a marked reduction in the number of calcific nodules. FGF-2 interrupted the \u2018canonical\u2019 TGF-\u03b2 signalling pathway, reducing the nuclear translocation of the SMAD2\/3 complex. The panel of genes assayed revealed that FGF-2 promoted a quiescent-type pattern of gene expression, with significant downregulations in typical myofibroblast markers \u03b1 smooth muscle actin, extracellular matrix proteins, and scleraxis. We did not see evidence of osteoblast differentiation: neither matrix-type calcification nor changes in osteoblast associated gene expression were observed. Our findings show that FGF-2 can reverse the myofibroblastic phenotype of VICs isolated from diseased valves and inhibit the calcification potential of these cells.<\/jats:p>","DOI":"10.1371\/journal.pone.0270227","type":"journal-article","created":{"date-parts":[[2022,6,17]],"date-time":"2022-06-17T17:26:59Z","timestamp":1655486819000},"page":"e0270227","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":14,"title":["Fibroblast growth factor 2 inhibits myofibroblastic activation of valvular interstitial 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