{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T09:17:51Z","timestamp":1778923071874,"version":"3.51.4"},"reference-count":47,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T00:00:00Z","timestamp":1768348800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T00:00:00Z","timestamp":1768348800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1R01DC020730"],"award-info":[{"award-number":["1R01DC020730"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1R01DC021453"],"award-info":[{"award-number":["1R01DC021453"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Laryngoscope"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Traditionally, disorders of the vocal fold (VF) mucosa and underlying musculature have been regarded as mutually exclusive entities. However, emerging evidence from other organ systems suggests mucosal and muscle compartments engage in reciprocal interactions with functional consequences. We hypothesized that similar crosstalk exists in the VF, whereby fibrotic mucosa influences adjacent muscle. To model this process, we stimulated human VF fibroblasts (HVOX) with TGF\u2010\u03b21, a central mediator of fibrosis, and examined the effects on rat VF myoblasts (rVF\u2010Mbs), as well as reciprocal influences of rVF\u2010Mbs on fibroblasts.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>HVOX fibroblasts were stimulated with 10\u2009ng\/mL TGF\u2010\u03b21, and the effects on rVF\u2010Mbs were assessed using conditioned media and co\u2010culture. Myotube formation was evaluated by immunofluorescence, and nuclear localization of Smad2\/3 was examined in conditioned media experiments. qRT\u2010PCR quantified transcripts related to myogenic differentiation and Smad2\/3 signaling. ALK4\/5 inhibition was performed in co\u2010culture to test TGF\u2010\u03b2\/Smad2\/3\u2010signaling pathway involvement. Reciprocal effects were examined by changes in fibrogenic gene expression in HVOX fibroblasts.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Both conditioned media and co\u2010culture suppressed myogenic differentiation in rVF\u2010Mbs; increased inhibition was observed in co\u2010culture, as indicated by reduced myotube formation, decreased Myh2 expression, and activation of Smad2\/3 signaling. ALK4\/5 inhibition abrogated these effects. Differentiating rVF\u2010Mbs attenuated the fibrogenic phenotype of HVOX fibroblasts.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Fibrotic VF mucosal cells can impair myogenic differentiation through TGF\u2010\u03b2\/Smad2\/3\u2010mediated fibroblast\u2013myoblast crosstalk, and myogenic cells may exert reciprocal anti\u2010fibrotic effects. These findings suggest mucosa\u2013muscle interactions may contribute to VF pathology and highlight Smad2\/3 as a potential therapeutic target.<\/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>\n                  <jats:sec>\n                    <jats:title>Study Design<\/jats:title>\n                    <jats:p>In vitro.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/lary.70366","type":"journal-article","created":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T12:00:22Z","timestamp":1768392022000},"page":"2638-2647","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>TGF\u03b2<\/scp>\n                    \/Smad2\/3\u2010Mediated Crosstalk Between Vocal Fold Fibroblasts and 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":[{"role":"author","vocabulary":"crossref"}]},{"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":[{"role":"author","vocabulary":"crossref"}]},{"given":"Renjie","family":"Bing","sequence":"additional","affiliation":[{"name":"Otolaryngology\u2010Head and Neck Surgery NYU Grossman School of Medicine  New York New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7577-0267","authenticated-orcid":false,"given":"Aaron M.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Otolaryngology\u2010Head and Neck Surgery NYU Grossman School of Medicine  New York New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryan C.","family":"Branski","sequence":"additional","affiliation":[{"name":"Otolaryngology\u2010Head and Neck Surgery NYU Grossman School of Medicine  New York New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,1,14]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1044\/2024_AJSLP-23-00407"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/lary.23189"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20102551"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0892-1997(02)00078-4"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/lary.25398"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1177\/0003489419826133"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1177\/000348949710600702"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/coa.13936"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2015"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.02.053"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.064162"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2015.198"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.01167.2011"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1177\/00034894211028497"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a022293"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.23.12457"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/lary.32474"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1177\/000348940911800310"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1039\/D0NA00268B"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2019.09.003"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1160\/TH08-05-0273"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00114.2011"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.70322\/jrbtm.2025.10001"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12079-009-0083-1"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.22783"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/lary.20174"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0115389"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvu264"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.7717\/peerj.4939"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-169X.2010.01209.x"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2016.09.010"},{"key":"e_1_2_9_34_1","article-title":"Co\u2010Culture With Normal and Senescent AC16 Cardiomyocytes Modulates Fibrotic Response in Primary Human Ventricular Fibroblasts","volume":"10","author":"Hidalgo V.","year":"2023","journal-title":"microPublication Biology"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2019-0245OC"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cger.2018.01.010"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00019.2003"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/lary.23589"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1369\/jhc.6R6995.2006"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.07.011"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2016.02.002"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201109091"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/376191"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1177\/03635465010290040201"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a021873"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a022137"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1097\/BOR.0b013e32834b3309"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.01180-14"}],"container-title":["The Laryngoscope"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/lary.70366","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/lary.70366","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/lary.70366","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T08:47:14Z","timestamp":1778921234000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/lary.70366"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,14]]},"references-count":47,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,6]]}},"alternative-id":["10.1002\/lary.70366"],"URL":"https:\/\/doi.org\/10.1002\/lary.70366","archive":["Portico"],"relation":{},"ISSN":["0023-852X","1531-4995"],"issn-type":[{"value":"0023-852X","type":"print"},{"value":"1531-4995","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,14]]},"assertion":[{"value":"2025-10-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-02","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}