{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T12:21:47Z","timestamp":1780316507273,"version":"3.54.1"},"reference-count":32,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2012,1,12]],"date-time":"2012-01-12T00:00:00Z","timestamp":1326326400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004085","name":"Ministry of Education, Science, and Technology","doi-asserted-by":"crossref","award":["A090084"],"award-info":[{"award-number":["A090084"]}],"id":[{"id":"10.13039\/501100004085","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Ministry for Health, Welfare & Family Affairs, Republic of Korea","award":["2010-0010279"],"award-info":[{"award-number":["2010-0010279"]}]},{"name":"Ministry for Health, Welfare & Family Affairs, Republic of Korea","award":["A090084"],"award-info":[{"award-number":["A090084"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin Experimental Allergy"],"published-print":{"date-parts":[[2012,6]]},"abstract":"Summary<\/jats:title>Background<\/jats:title>Nasal polyposis is a multi\u2010factorial disease associated with chronic inflammatory condition of the paranasal sinuses. Myofibroblast differentiation and extracellular matrix (ECM<\/jats:styled-content>) accumulation are involved in the pathogenesis of nasal polyposis.<\/jats:p><\/jats:sec>Objective<\/jats:title>The aim of this study was to study the effect of trichostatin A (TSA<\/jats:styled-content>), a histone deacetylase (HDAC<\/jats:styled-content>) inhibitor, on transforming growth factor (TGF<\/jats:styled-content>)\u2010\u03b21\u2010induced myofibroblast differentiation and ECM<\/jats:styled-content> accumulation in nasal polyp\u2010derived fibroblasts (NPDF<\/jats:styled-content>s).<\/jats:p><\/jats:sec>Methods<\/jats:title>Nasal polyp\u2010derived fibroblasts were isolated from nasal polyps of patients who have chronic rhinosinusitis with nasal polyp. TSA<\/jats:styled-content> was treated in TGF<\/jats:styled-content>\u2010\u03b21\u2010induced NPDF<\/jats:styled-content>s. Expression levels of HDAC<\/jats:styled-content>2, \u03b1\u2010smooth muscle actin (SMA<\/jats:styled-content>), TGF<\/jats:styled-content>\u2010\u03b21, collagen type I, acetylated Histone H3, acetylated Histone H4, phosphorylated Smad2\/3 and Smad7 were determined by RT<\/jats:styled-content>\u2010PCR<\/jats:styled-content>, western blot and\/or immunofluorescent staining. The total collagen amount production was analysed by Sircol soluble collagen assay and contractile activity was measured by collagen gel contraction assay. HDAC<\/jats:styled-content>2 inhibition by TSA<\/jats:styled-content> or HDAC<\/jats:styled-content>2 silencing was established by RT<\/jats:styled-content>\u2010PCR<\/jats:styled-content> and western blot. The epigenetic effect on \u03b1\u2010SMA<\/jats:styled-content> gene inactivation was examined by chromatin immunoprecipitation assay. Proliferation was determined by Ki67\u2010positive cell staining and cytotoxicity was assessed by 3\u2010(4,5\u2010 dimethylthiazol\u20102yl)\u20102,5\u2010diphenyl\u20102H\u2010tetrazolium bromide (MTT<\/jats:styled-content>) assay.<\/jats:p><\/jats:sec>Results<\/jats:title>The expression levels of HDAC<\/jats:styled-content>2, \u03b1\u2010SMA<\/jats:styled-content> and TGF<\/jats:styled-content>\u2010\u03b21 were increased in nasal polyp tissues compared to normal inferior turbinate tissues. TSA<\/jats:styled-content> and HDAC<\/jats:styled-content>2 silencing inhibited expression levels \u03b1\u2010SMA<\/jats:styled-content>, collagen and HDAC<\/jats:styled-content>2. TSA<\/jats:styled-content> induced hyperacetylation of histone and suppressed opening of \u03b1\u2010SMA<\/jats:styled-content> gene promoter in TGF<\/jats:styled-content>\u2010\u03b21\u2010induced NPDF<\/jats:styled-content>s. TSA<\/jats:styled-content> inhibited TGF<\/jats:styled-content>\u2010\u03b21\u2010induced Smad 2\/3 and rescued TGF<\/jats:styled-content>\u2010\u03b21\u2010suppressed Smad7 signalling pathway. Finally, TSA<\/jats:styled-content> blocked proliferation in TGF<\/jats:styled-content>\u2010\u03b21\u2010induced NPDF<\/jats:styled-content>s and has no cytotoxic effect in NPDF<\/jats:styled-content>s.<\/jats:p><\/jats:sec>Conclusions and Clinical Relevance<\/jats:title>These results suggest that HDAC<\/jats:styled-content> inhibition is associated with myofibroblast differentiation and extracelluar matrix accumulation in nasal polyposis. TSA<\/jats:styled-content> may be useful as an inhibitor of nasal polyp growth, and thus has potential to be used as a novel treatment option for nasal polyposis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/j.1365-2222.2011.03931.x","type":"journal-article","created":{"date-parts":[[2012,1,13]],"date-time":"2012-01-13T04:02:25Z","timestamp":1326427345000},"page":"872-882","source":"Crossref","is-referenced-by-count":63,"title":["Epigenetic regulation of myofibroblast differentiation and extracellular matrix production in nasal polyp\u2010derived fibroblasts"],"prefix":"10.1111","volume":"42","author":[{"given":"J.\u2010S.","family":"Cho","sequence":"first","affiliation":[{"name":"Brain Korea 21 Project for Biomedical Science College of Medicine Korea University Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.\u2010M.","family":"Moon","sequence":"additional","affiliation":[{"name":"Brain Korea 21 Project for Biomedical Science College of Medicine Korea University Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I.\u2010H.","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2010Head and Neck Surgery College of Medicine Korea University Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.\u2010Y.","family":"Um","sequence":"additional","affiliation":[{"name":"Brain Korea 21 Project for Biomedical Science College of Medicine Korea University Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.\u2010H.","family":"Moon","sequence":"additional","affiliation":[{"name":"Brain Korea 21 Project for Biomedical Science College of Medicine Korea University Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.\u2010J.","family":"Park","sequence":"additional","affiliation":[{"name":"Brain Korea 21 Project for Biomedical Science College of Medicine Korea University Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. 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