{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T13:06:14Z","timestamp":1786539974669,"version":"build-2736575974"},"reference-count":41,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2017,5,20]],"date-time":"2017-05-20T00:00:00Z","timestamp":1495238400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"National Institutes of Health\/National Institute on Deafness of and Other Communication Disorders","award":["RO1 DC013277"],"award-info":[{"award-number":["RO1 DC013277"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Laryngoscope"],"published-print":{"date-parts":[[2017,9]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Recent reports highlight the efficacy of small interfering RNA (siRNA) targeting <jats:italic>SMAD3<\/jats:italic> to regulate transforming growth factor \u03b2 (TGF\u2010\u03b2)\u2010mediated fibroplasia in vocal fold fibroblasts. The current study sought to investigate <jats:italic>SMAD3<\/jats:italic> expression during wound healing in vivo and quantify the downstream transcriptional events associated with <jats:italic>SMAD3<\/jats:italic> knockdown in vitro.<\/jats:p><\/jats:sec><jats:sec><jats:title>Study Design<\/jats:title><jats:p>In vivo and in vitro.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Unilateral vocal fold injury was created in a rabbit model. <jats:italic>SMAD3<\/jats:italic> and <jats:italic>SMAD7<\/jats:italic> mRNA expression was quantified at 1 hour and 1, 3, 7, 14, 30, 60, and 90 days following injury. In vitro, multi\u2010gene analysis technology was employed in our immortalized human vocal\u2010fold fibroblast cell line following TGF\u2010\u03b21 stimulation\u2009\u00b1\u2009<jats:italic>SMAD3<\/jats:italic> knockdown across time points.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:italic>SMAD3<\/jats:italic> mRNA expression increased following injury; upregulation was significant at 3 and 7 days compared to control (both <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001). <jats:italic>SMAD7<\/jats:italic> mRNA was also upregulated at 3, 7, and 14 days (<jats:italic>P<\/jats:italic>\u2009=\u20090.02, <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001, and <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001, respectively). In vitro, <jats:italic>SMAD3<\/jats:italic> knockdown reduced the expression of multiple profibrotic, TGF\u2010\u03b2 signaling, and extracellular matrix metabolism genes at 6 and 24 hours following TGF\u2010\u03b21 stimulation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Cumulatively, these data support <jats:italic>SMAD3<\/jats:italic> as a potential master regulator of TGF\u2010\u03b2\u2010mediated fibrosis. <jats:italic>SMAD3<\/jats:italic> transcription peaked 7 days following injury. Multi\u2010gene analysis indicated that the therapeutic effectiveness of <jats:italic>SMAD3<\/jats:italic> knockdown may be related to regulation of downstream mediators of fibroplasia and altered TGF\u2010\u03b2 signaling.<\/jats:p><\/jats:sec><jats:sec><jats:title>Level of Evidence<\/jats:title><jats:p>NA. <jats:italic>Laryngoscope<\/jats:italic>, 127:E308\u2013E316, 2017<\/jats:p><\/jats:sec>","DOI":"10.1002\/lary.26648","type":"journal-article","created":{"date-parts":[[2017,5,23]],"date-time":"2017-05-23T22:06:31Z","timestamp":1495577191000},"source":"Crossref","is-referenced-by-count":19,"title":["<scp><i>SMAD<\/i><\/scp><i>3<\/i> expression and regulation of fibroplasia in vocal fold injury"],"prefix":"10.1002","volume":"127","author":[{"given":"Nao","family":"Hiwatashi","sequence":"first","affiliation":[{"name":"NYU Voice Center, Department of Otolaryngology\u2013Head and Neck Surgery New York University School of Medicine New York New York U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter A.","family":"Benedict","sequence":"additional","affiliation":[{"name":"NYU Voice Center, Department of Otolaryngology\u2013Head and Neck Surgery New York University School of Medicine New York New York U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory R.","family":"Dion","sequence":"additional","affiliation":[{"name":"NYU Voice Center, Department of Otolaryngology\u2013Head and Neck Surgery New York University School of Medicine New York New York U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renjie","family":"Bing","sequence":"additional","affiliation":[{"name":"NYU Voice Center, Department of Otolaryngology\u2013Head and Neck Surgery New York University School of Medicine New York New York U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iv","family":"Kraja","sequence":"additional","affiliation":[{"name":"NYU Voice Center, Department of Otolaryngology\u2013Head and Neck Surgery New York University School of Medicine New York New York U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milan R.","family":"Amin","sequence":"additional","affiliation":[{"name":"NYU Voice Center, Department of Otolaryngology\u2013Head and Neck Surgery 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":"NYU Voice Center, Department of Otolaryngology\u2013Head and Neck Surgery New York University School of Medicine New York New York U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,5,20]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1177\/019459989611500521"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvoice.2007.12.002"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)63486-4"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.2174\/1566523044578004"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.3181\/00379727-214-44066"},{"key":"e_1_2_6_7_1","first-page":"565","article-title":"Role of transforming growth factor beta in corneal function, biology and pathology","volume":"10","author":"Tandon A","year":"2010","journal-title":"Curr Mol Med"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.286.5441.950"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2742"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1001\/archoto.2010.107"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/lary.24723"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/lary.25673"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1177\/000348940010900206"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1080\/00016489950182043"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0892-1997(97)80083-5"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005537-199903000-00030"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1177\/000348940911800310"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/lary.26432"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1097\/MOO.0b013e32833fecd1"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1177\/000348940611501212"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.03-1273rev"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199411103311907"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/39369"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/abbs\/gmp018"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0959-9673.2004.00377.x"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.14.6.627"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-003-0706-5"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2001.25480"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2016.03.011"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1202052"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00437.2005"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M701991200"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.08-3223"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.21154"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1359-6101(97)00010-5"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2007-0174OC"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3003421"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1136\/thorax.58.9.772"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0076451"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1177\/000348940811700809"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200706-806OC"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80545-0"}],"container-title":["The Laryngoscope"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Flary.26648","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/lary.26648","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,4]],"date-time":"2023-10-04T02:02:24Z","timestamp":1696384944000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/lary.26648"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,5,20]]},"references-count":41,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2017,9]]}},"alternative-id":["10.1002\/lary.26648"],"URL":"https:\/\/doi.org\/10.1002\/lary.26648","archive":["Portico"],"relation":{},"ISSN":["0023-852X","1531-4995"],"issn-type":[{"value":"0023-852X","type":"print"},{"value":"1531-4995","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,5,20]]}}}