{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T02:26:03Z","timestamp":1780971963880,"version":"3.54.1"},"reference-count":51,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T00:00:00Z","timestamp":1753833600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T00:00:00Z","timestamp":1753833600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000055","name":"National Institute on Deafness and Other Communication Disorders","doi-asserted-by":"publisher","award":["1R01DC021453"],"award-info":[{"award-number":["1R01DC021453"]}],"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":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background\/Objectives<\/jats:title>\n                    <jats:p>Vocal fold (VF) muscle atrophy, often associated with neuromuscular disorders and aging, can lead to voice\u2010related disability. Myostatin is well\u2010known to mediate skeletal muscle atrophy via Smad2\/3 signaling, whereas TGF\u2010\u03b21, a potent inducer of Smad2\/3 signaling, is upregulated following VF injury. However, the impact of Smad2\/3 signaling on laryngeal muscles remains unclear. This study provides foundational insight regarding Smad2\/3\u2010dependent atrophic responses of VF skeletal muscle cells, to ultimately develop novel therapeutic strategies for VF muscle atrophy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Study Design<\/jats:title>\n                    <jats:p>In vitro.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Myoblasts isolated from the rat thyroarytenoid muscle were differentiated into myotubes in myogenic differentiation medium \u00b1500\u2009ng\/mL myostatin or 10\u2009ng\/mL TGF\u2010\u03b21, in the presence or absence of an ALK4\/5 inhibitor or siRNA targeting Smad2 and Smad3. Myotube formation and activation of Smad2\/3 (nuclear localization of Smad2\/3) were assessed via immunofluorescence. Transcription related to myotube differentiation and Smad2\/3 signaling was quantified by qRT\u2010PCR.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Both myostatin and TGF\u2010\u03b21 suppressed myogenic differentiation, increased Smad2\/3 nuclear intensity, downregulated\n                      <jats:italic>Myh2<\/jats:italic>\n                      , and upregulated downstream targets of Smad2\/3 (\n                      <jats:italic>Ccn2<\/jats:italic>\n                      and\n                      <jats:italic>Serpine1<\/jats:italic>\n                      ) and\n                      <jats:italic>Fbox32<\/jats:italic>\n                      , an atrophy\u2010related gene. These effects were more pronounced with TGF\u2010\u03b21 than with myostatin and were reversed by inhibition of ALK4\/5. Furthermore, Smad2\/3 knockdown via siRNA promoted myogenic differentiation, further supporting the role of Smad2\/3 signaling in the atrophic response in VF myoblasts.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Smad2\/3 signaling mediates differentiation of VF myoblasts and TGF\u2010\u03b21, a potent mediator of fibrosis, elicited a more pronounced atrophic response than myostatin. Smad2\/3 may be an attractive therapeutic target for VF muscle atrophy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Level of Evidence<\/jats:title>\n                    <jats:p>NA.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/lary.32474","type":"journal-article","created":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T09:45:19Z","timestamp":1753868719000},"page":"291-303","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Smad2\/3 Signaling Mediates the Atrophic Response in Vocal Fold Myoblasts In\u00a0Vitro"],"prefix":"10.1002","volume":"136","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3010-5618","authenticated-orcid":false,"given":"Masayoshi","family":"Yoshimatsu","sequence":"first","affiliation":[{"name":"Otolaryngology\u2010Head and Neck Surgery NYU Grossman School of Medicine  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0061-2114","authenticated-orcid":false,"given":"Ryosuke","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Otolaryngology\u2010Head and Neck Surgery NYU Grossman School of Medicine  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renjie","family":"Bing","sequence":"additional","affiliation":[{"name":"Otolaryngology\u2010Head and Neck Surgery NYU Grossman School of Medicine  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5362-0866","authenticated-orcid":false,"given":"Gary J.","family":"Gartling","sequence":"additional","affiliation":[{"name":"Otolaryngology\u2010Head and Neck Surgery NYU Grossman School of Medicine  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan C.","family":"Branski","sequence":"additional","affiliation":[{"name":"Otolaryngology\u2010Head and Neck Surgery NYU Grossman School of Medicine  New York New York 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