{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T22:07:17Z","timestamp":1790633237101,"version":"4.1.0"},"reference-count":36,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,8,4]],"date-time":"2017-08-04T00:00:00Z","timestamp":1501804800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,8,4]],"date-time":"2017-08-04T00:00:00Z","timestamp":1501804800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>To investigate the potential role of vitamin D (1,25(OH)<jats:sub>2<\/jats:sub>D<jats:sub>3<\/jats:sub>) in preventing the development of nasal polyps, we examined the effect of vitamin D on myofibroblast differentiation and extracellular matrix (ECM) production in TGF-\u03b21-induced nasal polyp-derived fibroblasts (NPDFs) and elucidated the mechanisms underlying its inhibitory effect. 1,25(OH)<jats:sub>2<\/jats:sub>D<jats:sub>3<\/jats:sub> significantly reduced expression levels of \u03b1-SMA, a myofibroblast marker, and fibronectin, a representative ECM component, in a dose-dependent manner in TGF-\u03b21-induced\u00a0NPDFs. 1,25(OH)<jats:sub>2<\/jats:sub>D<jats:sub>3<\/jats:sub> suppressed activated Smad2\/3 in time-course. Up-regulation of \u03b1-SMA, fibronectin and phosphorylation of Smad2\/3 by TGF-\u03b21 was unaffected by 1,25(OH)<jats:sub>2<\/jats:sub>D<jats:sub>3<\/jats:sub> in NPDFs after vitamin D receptor-specific siRNA transfection. We confirmed that the Smad2\/3-specific inhibitor SIS3 inactivated Smad2\/3 and reduced \u03b1-SMA and fibronectin expression. Furthermore, acetylation of histone H3 was compromised by 1,25(OH)<jats:sub>2<\/jats:sub>D<jats:sub>3,<\/jats:sub> leading to inhibition of <jats:italic>collagen 1A1<\/jats:italic>, <jats:italic>collagen 1A2<\/jats:italic> and <jats:italic>\u03b1-SMA<\/jats:italic> gene expression. Treatment with 1,25(OH)<jats:sub>2<\/jats:sub>D<jats:sub>3<\/jats:sub> also significantly suppressed TGF-\u03b21-enhanced contractility and motility in a contraction assay and Transwell migration assay. Finally, 1,25(OH)<jats:sub>2<\/jats:sub>D<jats:sub>3<\/jats:sub> had a similar effect in <jats:italic>ex vivo<\/jats:italic> organ cultures of nasal polyps. Taken together, our results suggest that 1,25(OH)<jats:sub>2<\/jats:sub>D<jats:sub>3<\/jats:sub> might be an effective therapy for nasal polyps by reducing myofibroblast differentiation and ECM production mediated by Smad2\/3-dependent TGF-\u03b21 signaling pathways in NPDFs.<\/jats:p>","DOI":"10.1038\/s41598-017-07561-6","type":"journal-article","created":{"date-parts":[[2017,7,31]],"date-time":"2017-07-31T11:03:33Z","timestamp":1501499013000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Vitamin D attenuates myofibroblast differentiation and extracellular matrix accumulation in nasal polyp-derived fibroblasts through smad2\/3 signaling pathway"],"prefix":"10.1038","volume":"7","author":[{"given":"Seoung-Ae","family":"Lee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun-Woo","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji-Young","family":"Um","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae-Min","family":"Shin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7011-6071","authenticated-orcid":false,"given":"Il-Ho","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heung-Man","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,8,4]]},"reference":[{"key":"7561_CR1","doi-asserted-by":"publisher","first-page":"507","DOI":"10.2147\/TCRM.S2379","volume":"4","author":"JR Newton","year":"2008","unstructured":"Newton, J. 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