{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T16:06:10Z","timestamp":1792253170268,"version":"4.4.0"},"reference-count":34,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2018,10,16]],"date-time":"2018-10-16T00:00:00Z","timestamp":1539648000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000055","name":"National Institute on Deafness and Other Communication Disorders","doi-asserted-by":"publisher","award":["RO1 DC013277"],"award-info":[{"award-number":["RO1 DC013277"]}],"id":[{"id":"10.13039\/100000055","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000055","name":"National Institute on Deafness and Other Communication Disorders","doi-asserted-by":"publisher","award":["DC DC017397"],"award-info":[{"award-number":["DC DC017397"]}],"id":[{"id":"10.13039\/100000055","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Laryngoscope"],"published-print":{"date-parts":[[2019,5]]},"abstract":"<jats:sec><jats:title>Objectives\/Hypothesis<\/jats:title><jats:p>Direct glucocorticoid (GC) injection for vocal fold (VF) scarring has evolved as a therapeutic strategy, but the mechanisms underlying the antifibrotic effects remain unclear. GCs act via the glucocorticoid receptor (GR), which is phosphorylated at multiple serine residues in a hormone\u2010dependent manner to affect bioactivity. We hypothesize that GCs regulate SMAD signaling via GR phosphorylation in vocal fold fibroblasts (VFFs).<\/jats:p><\/jats:sec><jats:sec><jats:title>Study Design<\/jats:title><jats:p>In vitro.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Human VFFs were treated with dexamethasone (DM; 10<jats:sup>\u22125<\/jats:sup>\u201310<jats:sup>\u22127<\/jats:sup>M)\u2009\u00b1\u2009transforming growth factor (TGF)\u2010\u03b21 (10\u2009ng\/mL). RU486 (10<jats:sup>\u22126<\/jats:sup>M) was employed to isolate the regulatory effects of GR. Total GR, Ser<jats:sup>211<\/jats:sup>, and Ser<jats:sup>203<\/jats:sup> phosphorylation was examined via sodium dodecyl sulfate\u2010polyacrylamide gel electrophoresis and immunocytochemistry. Quantitative polymerase chain reaction was employed to determine GR\u2010mediated effects of DM on genes related to fibrosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Total GR and Ser<jats:sup>211<\/jats:sup> phosphorylation was observed predominantly in the nucleus 1 hour after DM administration. DM decreased total GR expression, but Ser<jats:sup>203<\/jats:sup> and Ser<jats:sup>211<\/jats:sup> phosphorylation increased. RU486 limited the effects of DM. <jats:italic>SMAD3<\/jats:italic> and <jats:italic>SMAD7<\/jats:italic> mRNA expression significantly decreased 4 hours after DM administration (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05); this response was negated by RU486. <jats:italic>COL1A1<\/jats:italic> remained unchanged, and <jats:italic>ACTA2<\/jats:italic> significantly increased following 24 hours of DM treatment (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>DM regulated TGF\u2010\u03b21 signaling via altered <jats:italic>SMAD3<\/jats:italic> and <jats:italic>SMAD7<\/jats:italic> expression. This response was associated with altered GR phosphorylation. These findings provide insight into the mechanisms of steroidal effects on vocal fold repair; ultimately, we seek to enhance therapeutic strategies for these challenging patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Level of Evidence<\/jats:title><jats:p>NA <jats:italic>Laryngoscope<\/jats:italic>, 129:E187\u2013E193, 2019<\/jats:p><\/jats:sec>","DOI":"10.1002\/lary.27570","type":"journal-article","created":{"date-parts":[[2018,10,16]],"date-time":"2018-10-16T13:07:25Z","timestamp":1539695245000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Phosphorylation of the glucocorticoid receptor alters <i>SMAD<\/i> signaling in vocal fold fibroblasts"],"prefix":"10.1002","volume":"129","author":[{"given":"Shigeyuki","family":"Mukudai","sequence":"first","affiliation":[{"name":"From the Department of Otolaryngology\u2013Head and Neck Surgery  NYU Voice Center  New York New York U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nao","family":"Hiwatashi","sequence":"additional","affiliation":[{"name":"From the Department of Otolaryngology\u2013Head and Neck Surgery  NYU Voice Center  New York New York U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renjie","family":"Bing","sequence":"additional","affiliation":[{"name":"From the Department of Otolaryngology\u2013Head and Neck Surgery  NYU Voice Center  New York New York U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Garabedian","sequence":"additional","affiliation":[{"name":"the Department of Microbiology  New York University School of Medicine  New York New York U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1190-9036","authenticated-orcid":false,"given":"Ryan C.","family":"Branski","sequence":"additional","affiliation":[{"name":"From the Department of Otolaryngology\u2013Head and Neck Surgery  NYU Voice Center  New York New York U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,10,16]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvoice.2007.12.002"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.moo.0000162261.49739.b7"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1177\/019459989611500521"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.mlg.0000231455.19183.8c"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1808-8694(15)30155-5"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvoice.2013.04.015"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/lary.24556"},{"key":"e_1_2_6_9_1","first-page":"301","article-title":"Fibroblasts and myofibroblasts in wound healing","volume":"7","author":"Darby IA","year":"2014","journal-title":"Clin Cosmet Investig Dermatol"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/lary.25673"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1021412601538"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1022683010976"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2014-1605"},{"key":"e_1_2_6_14_1","doi-asserted-by":"crossref","first-page":"11236","DOI":"10.1016\/S0021-9258(18)90853-7","article-title":"Glucocorticoid receptors in human fibroblasts derived from normal dermis and keloid tissue","volume":"259","author":"Gadson PF","year":"1984","journal-title":"J Biol Chem"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/lary.21920"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-0760(97)00185-4"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2005-0235"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110530200"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/lary.26678"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.21.11776"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1177\/000348940911800310"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1177\/000348940611501212"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.03-1273rev"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199411103311907"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1677\/joe.1.05962"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA118.002540"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2016-1829"},{"key":"e_1_2_6_28_1","first-page":"1479","article-title":"Effect of IFN\u2010gamma and dexamethasone on TGF\u2010beta1\u2010induced human fetal lung fibroblast\u2010myofibroblast differentiation","volume":"25","author":"Gu L","year":"2004","journal-title":"Acta Pharmacol Sin"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1177\/000348949910800203"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/ppul.1081"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201506-1063ST"},{"key":"e_1_2_6_32_1","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1136\/thx.35.8.593","article-title":"Cryptogenic fibrosing alveolitis: response to corticosteroid treatment and its effect on survival","volume":"35","author":"Turner\u2010Warwick M","year":"1980","journal-title":"Thorax"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.161.2.ats3-00"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.163.1.17"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2008.06.046"}],"container-title":["The Laryngoscope"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Flary.27570","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/lary.27570","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/lary.27570","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/lary.27570","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,10]],"date-time":"2023-09-10T16:23:23Z","timestamp":1694363003000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/lary.27570"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,10,16]]},"references-count":34,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2019,5]]}},"alternative-id":["10.1002\/lary.27570"],"URL":"https:\/\/doi.org\/10.1002\/lary.27570","archive":["Portico"],"relation":{},"ISSN":["0023-852X","1531-4995"],"issn-type":[{"value":"0023-852X","type":"print"},{"value":"1531-4995","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,10,16]]},"assertion":[{"value":"2018-03-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-08-20","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-10-16","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}