{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T19:10:55Z","timestamp":1770059455039,"version":"3.49.0"},"reference-count":26,"publisher":"S. Karger AG","issue":"4","license":[{"start":{"date-parts":[[2012,1,1]],"date-time":"2012-01-01T00:00:00Z","timestamp":1325376000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2012,1,1]],"date-time":"2012-01-01T00:00:00Z","timestamp":1325376000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int Arch Allergy Immunol"],"published-print":{"date-parts":[[2012]]},"abstract":"<b><i>Background:<\/i><\/b> Chronic hypoxia is associated with remodeling in various organs. Reactive oxygen species (ROS) derived from NADPH oxidases (Nox), and transforming growth factor-\u03b2<sub>1<\/sub> (TGF-\u03b2<sub>1<\/sub>) have been implicated in the pathogenesis of hypoxia-induced remodeling. The aims of this study were to determine in hypoxia-stimulated nasal polyp-derived fibroblasts (NPDF) the effect of hypoxia on the differentiation of myofibroblasts, the role of ROS, the major Nox homolog mediating myofibroblast differentiation, and the role of TGF-\u03b2<sub>1<\/sub>. <b><i>Methods:<\/i><\/b> Eight primary cultures of NPDF were established from nasal polyps, which were incubated under hypoxic conditions. Reverse transcription polymerase chain reaction for \u03b1<i>SMA, Nox1, Nox3, Nox4, Nox5, <\/i>and <i>fibronectin <\/i>mRNA was performed. Western blotting for \u03b1-SMA and fibronectin was done. ROS production was detected using a fluorometer. NPDF were pretreated with ROS scavengers and transfected with <i>siNox4<\/i>. The TGF-\u03b2<sub>1<\/sub> protein level was measured by ELISA. The effect of treatment with TGF-\u03b2<sub>1<\/sub> type I tyrosine kinase inhibitor SB431542 on myofibroblast differentiation was observed. <b><i>Results:<\/i><\/b> Hypoxic stimulation of NPDF significantly increased \u03b1-SMA and fibronectin mRNA and protein expression. ROS production was increased by hypoxia, and ROS scavengers inhibited myofibroblast differentiation. <i>Nox4 <\/i>mRNA was the only Nox homolog increased by hypoxia. Transfection with <i>siNox4 <\/i>inhibited myofibroblast differentiation. TGF-\u03b2<sub>1<\/sub> was secreted endogenously by hypoxic NPDF. SB431542 significantly inhibited myofibroblast differentiation. <b><i>Conclusions:<\/i><\/b> Hypoxia induces myofibroblast differentiation of NPDF through a signaling pathway involving Nox4-dependent ROS generation and TGF-\u03b2<sub>1<\/sub>. Therapies targeting Nox4 may be effective against remodeling of nasal polyps.<\/jats:p>","DOI":"10.1159\/000337658","type":"journal-article","created":{"date-parts":[[2012,7,27]],"date-time":"2012-07-27T23:08:30Z","timestamp":1343430510000},"page":"399-409","source":"Crossref","is-referenced-by-count":18,"title":["Nox4 Mediates Hypoxia-Stimulated Myofibroblast Differentiation in Nasal Polyp-Derived Fibroblasts"],"prefix":"10.1159","volume":"159","author":[{"given":"You-Mi","family":"Moon","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hee Joon","family":"Kang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jung-Sun","family":"Cho","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Il-Ho","family":"Park","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heung-Man","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"127","published-online":{"date-parts":[[2012,7,26]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1097%2F00130832-200302000-00001"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1097%2F00005537-199602000-00017"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1056%2FNEJM200005043421807"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1097%2F00005537-199707000-00018"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1097%2FACI.0b013e3282f3f488"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1016%2Fj.amjoto.2010.11.010"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1111%2Fj.1478-3231.2010.02205.x"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1152%2Fajplung.00007.2009"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1097%2FMLG.0b013e31802e927b"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1074%2Fjbc.M502412200"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1074%2Fjbc.M803964200"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1161%2F01.RES.0000190403.87462.bf"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1152%2Fajplung.90488.2008"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1161%2F01.RES.86.5.494"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1016%2Fj.freeradbiomed.2007.11.016"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1161%2F01.RES.0000187457.24338.3D"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1152%2Fajplung.00269.2005"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1161%2FCIRCRESAHA.107.148015"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1146%2Fannurev.cb.06.110190.003121"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1016%2Fj.imlet.2006.01.003"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1034%2Fj.1600-0897.2002.01090.x"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1152%2Fjapplphysiol.00595.2005"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.1080%2F0036554021000028113"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.1161%2F01.RES.0000243584.45145.3f"},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.1097%2FMLG.0b013e318159cc0b"},{"key":"ref26","doi-asserted-by":"publisher","DOI":"10.1165%2Frcmb.2003-0071OC"}],"container-title":["International Archives of Allergy and Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/337658","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/337658","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T18:13:12Z","timestamp":1745431992000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000337658"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012]]},"references-count":26,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2012,11,1]]},"published-print":{"date-parts":[[2012,11,16]]}},"URL":"https:\/\/doi.org\/10.1159\/000337658","archive":["Portico"],"relation":{},"ISSN":["1018-2438","1423-0097"],"issn-type":[{"value":"1018-2438","type":"print"},{"value":"1423-0097","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012]]}}}