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Transforming growth factor\u2010\u03b2 (TGF\u2010\u03b2) is considered a master switch in the induction of the profibrotic program which can induce fibroblasts to synthesize and contract extracellular matrix (ECM) proteins. A previous study has shown TGF\u2010\u03b21 signaling and collagen overproduction in the CRSsNP, but the responsible cells and mechanism of action remain unclear. Therefore, this study was aimed to investigate the relationship between TGF\u2010\u03b21 stimulation and collagen expression and to explore the role of connective tissue growth factor (CTGF) during the remodeling process using human CRSsNP nasal mucosa tissues and mucosa\u2010derived fibroblasts as main materials. We found that TGF\u2010\u03b21 and its isoforms could promote collagen protein expression. Concomitantly, TGF\u2010\u03b21 caused CTGF expression and secretion. An addition of exogenous CTGF to fibroblasts also caused collagen expression. In accordance with these observations, TGF\u2010\u03b21, CTGF, and collagen were highly expressed in the subepithelial stroma region of CRSsNP nasal mucosa, as determined by immunohistochemistry. The TGF\u2010\u03b21\u2010mediated collagen expression could be blocked by actinomycin D and SIS3, suggesting that the induction was through transcriptional regulation and Smad2\/3\u2010dependent pathway. Finally, we demonstrated that CTGF small interfering RNA knockdown led to a substantial decrease in TGF\u2010\u03b21\u2010mediated collagen expression. Collectively, our results provide first and further evidence that TGF\u2010\u03b21 mediates collagen expression\u2013production through a canonical Smad2\/3\u2010dependent pathway and CTGF induction and secretion in human nasal fibroblasts. Moreover, TGF\u2010\u03b21, CTGF, and collagen are highly expressed in human CRSsNP nasal mucosa specimens, suggesting their roles in tissue remodeling during CRSsNP progression.<\/jats:p>","DOI":"10.1002\/jcp.27718","type":"journal-article","created":{"date-parts":[[2018,11,14]],"date-time":"2018-11-14T04:21:35Z","timestamp":1542169295000},"page":"10489-10499","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["TGF\u03b2 mediates collagen production in human CRSsNP nasal mucosa\u2010derived fibroblasts through Smad2\/3\u2010dependent pathway and CTGF induction and secretion"],"prefix":"10.1002","volume":"234","author":[{"given":"Jiunn\u2010Min","family":"Shieh","sequence":"first","affiliation":[{"name":"Department of Internal Medicine Chi\u2010Mei Medical Center Tainan Taiwan"},{"name":"Department of Recreation and Healthcare Management Chia Nan University of Pharmacy and Science Tainan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yih\u2010Jeng","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Head and Neck Surgery Shin Kong Wu Ho\u2010Su Memorial Hospital Taipei Taiwan"},{"name":"School of Medicine, College of Medicine, Fu Jen Catholic University New Taipei City Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessie Chao\u2010Yun","family":"Chi","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Head and Neck Surgery Taichung Hospital, Ministry of Health and Welfare Taichung Taiwan"},{"name":"Institute of Medicine, Chung Shan Medical University Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9248-5030","authenticated-orcid":false,"given":"Wen\u2010Bin","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Medicine, College of Medicine, Fu Jen Catholic University New Taipei City Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,11,13]]},"reference":[{"key":"e_1_2_8_1_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb826"},{"key":"e_1_2_8_1_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2013.02.036"},{"key":"e_1_2_8_1_4_1","doi-asserted-by":"publisher","DOI":"10.2500\/105065800781329573"},{"key":"e_1_2_8_1_5_1","doi-asserted-by":"publisher","DOI":"10.3109\/08977194.2011.595714"},{"key":"e_1_2_8_1_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1398-9995.1992.tb02242.x"},{"key":"e_1_2_8_1_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/ACI.0b013e32834233ef"},{"key":"e_1_2_8_1_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2222.2011.03898.x"},{"key":"e_1_2_8_1_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2009.04.013"},{"key":"e_1_2_8_1_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2008.02.018"},{"key":"e_1_2_8_1_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.20251"},{"key":"e_1_2_8_1_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/00002281-200111000-00010"},{"key":"e_1_2_8_1_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11882-009-0031-4"},{"key":"e_1_2_8_1_14_1","doi-asserted-by":"publisher","DOI":"10.1177\/1933719116687855"},{"key":"e_1_2_8_1_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1286-4579(99)00259-2"},{"key":"e_1_2_8_1_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-24340-z"},{"key":"e_1_2_8_1_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2006.07.044"},{"key":"e_1_2_8_1_18_1","doi-asserted-by":"publisher","DOI":"10.1136\/mp.54.3.180"},{"key":"e_1_2_8_1_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2010.02.023"},{"issue":"4","key":"e_1_2_8_1_20_1","first-page":"183","article-title":"Staging in rhinosinusitus","volume":"31","author":"Lund V. 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