{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T03:55:34Z","timestamp":1792468534124,"version":"4.5.0"},"reference-count":26,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2020,2,27]],"date-time":"2020-02-27T00:00:00Z","timestamp":1582761600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int Forum Allergy Rhinol"],"published-print":{"date-parts":[[2020,5]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>All\u2010<jats:italic>trans<\/jats:italic> retinoic acid (ATRA), a derivative of vitamin A, is known to have anti\u2010fibrogenic effects and regulates cell proliferation and differentiation. Therefore, these abilities of ATRA may influence tissue remodeling in the upper airway. The aims of the present study were to investigate the effects of ATRA on the myofibroblast differentiation, extracellular matrix (ECM) production, cell migration, and collagen gel contraction and to determine the molecular mechanisms of ATRA in TGF\u2010\u03b21\u2010induced nasal polyp\u2012derived fibroblasts (NPDFs).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>NPDFs were isolated from nasal polyp. Cytotoxicity was evaluated by 3\u2010(4,5\u2010dimethylthiazol\u20102yl)\u20102,5\u2010diphenyl\u2010tetrazolium bromide assay. TGF\u2010\u03b21\u2012induced fibroblasts were pretreated with ATRA. The expression levels of alpha\u2010smooth muscle actin (\u03b1\u2010SMA), collagen type 1, fibronectin, phospho\u2010mitogen\u2012activated protein kinase, and p\u2010p50 (nuclear factor\u2010kappaB [NF\u2010\u03baB]) were measured by Western blot analysis, real\u2010time polymerase chain reaction, and\/or immunofluorescence staining. Cell migration was analyzed with cell migration scratch assay and Transwell migration assay. Collagen contractile activity was measured using a collagen gel contraction assay.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>ATRA had no significant cytotoxic effect in NPDFs. Expression levels of \u03b1\u2010SMA, collagen type 1, and fibronectin stimulated by TGF\u2010\u03b21 were significantly downregulated in the ATRA\u2010pretreated fibroblasts. TGF\u2010\u03b21\u2012induced cell migration and collagen gel contraction were significantly inhibited by ATRA pretreatment. ATRA also significantly inhibited phosphorylation of c\u2010Jun N\u2010terminal kinase (JNK), p38, and p50 in TGF\u2010\u03b21\u2012induced NPDFs, but did not inhibit phosphorylation of extracellular signal\u2012related kinase (ERK).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>ATRA downregulated myofibroblast differentiation, ECM production, cell migration, and collagen gel contraction via p38, JNK\u2010dependent NF\u2010\u03baB\u2012signaling pathways in TGF\u2010\u03b21\u2012induced NPDFs. The findings suggest that ATRA could serve as a novel therapeutic agent to ameliorate nasal polyp development.<\/jats:p><\/jats:sec>","DOI":"10.1002\/alr.22525","type":"journal-article","created":{"date-parts":[[2020,2,27]],"date-time":"2020-02-27T11:20:30Z","timestamp":1582802430000},"page":"636-645","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["All\u2010<i>trans<\/i> retinoic acid regulates TGF\u2010\u03b21\u2012induced extracellular matrix production via p38, JNK, and NF\u2010\u03baB\u2012signaling pathways in nasal polyp\u2012derived fibroblasts"],"prefix":"10.1002","volume":"10","author":[{"given":"Su\u2010Jong","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology\u2012Head and Neck Surgery Guro Hospital, Korea University College of Medicine  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joo\u2010Hoo","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2012Head and Neck Surgery Guro Hospital, Korea University College of Medicine  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seoung\u2010Ae","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2012Head and Neck Surgery Guro Hospital, Korea University College of Medicine  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong\u2010Geun","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2012Head and Neck Surgery Guro Hospital, Korea University College of Medicine  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae\u2010Min","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2012Head and Neck Surgery Guro Hospital, Korea University College of Medicine  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heung\u2010Man","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2012Head and Neck Surgery Guro Hospital, Korea University College of Medicine  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,2,27]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1177\/00034894041130S502"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2009.12.989"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1472-9725.2003.00061.x"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.2500\/ajra.2014.28.4018"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.2500\/ajra.2013.27.3941"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1177\/194589240401800307"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005537-199707000-00018"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.2500\/ajra.2013.27.3827"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0025450"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-0436.2007.00206.x"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-12-3175"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.3892\/ijo.2014.2354"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.3109\/01902148.2011.646052"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2008.05.192"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2222.2011.03931.x"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.13-13572"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2013.11.010"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2009.12.980"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2008.01.006"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005537-200402000-00019"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2016.04.015"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.03-1273rev"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1071809"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00018.2011"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.14.1.649"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1186\/1479-5876-10-183"}],"container-title":["International Forum of Allergy &amp; 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