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| 標題: | TGF mediates collagen production in human CRSsNP nasal mucosa-derived fibroblasts through Smad2/3-dependent pathway and CTGF induction and secretion |
| 作者: | Jiunn-Min Shieh(謝俊民)
Tsai, Yih-Jeng
Chi, Jessie Chao-Yun
Wu, Wen-Bin |
| 貢獻者: | Chi Mei Med Ctr, Dept Internal Med
Chia Nan Univ Pharm & Sci, Dept Recreat & Healthcare Management
Shin Kong Wu Ho Mem Hosp, Dept Otolaryngol Head & Neck Surg
Fu Jen Catholic Univ, Sch Med, Coll Med
Minist Hlth & Welf, Taichung Hosp, Dept Otolaryngol Head & Neck Surg
Chung Shan Med Univ, Inst Med |
| 關鍵字: | cellular signaling
CRS
CTGF
extracellular matrix
tissue remodeling |
| 日期: | 2019-07 |
| 上傳時間: | 2020-07-29 13:49:08 (UTC+8) |
| 出版者: | WILEY |
| 摘要: | Chronic rhinosinusitis without nasal polyp (CRSsNP) is characterized by tissue remodeling and fibrosis. Transforming growth factor- (TGF-) 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-1 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-1 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-derived fibroblasts as main materials. We found that TGF-1 and its isoforms could promote collagen protein expression. Concomitantly, TGF-1 caused CTGF expression and secretion. An addition of exogenous CTGF to fibroblasts also caused collagen expression. In accordance with these observations, TGF-1, CTGF, and collagen were highly expressed in the subepithelial stroma region of CRSsNP nasal mucosa, as determined by immunohistochemistry. The TGF-1-mediated collagen expression could be blocked by actinomycin D and SIS3, suggesting that the induction was through transcriptional regulation and Smad2/3-dependent pathway. Finally, we demonstrated that CTGF small interfering RNA knockdown led to a substantial decrease in TGF-1-mediated collagen expression. Collectively, our results provide first and further evidence that TGF-1 mediates collagen expression-production through a canonical Smad2/3-dependent pathway and CTGF induction and secretion in human nasal fibroblasts. Moreover, TGF-1, CTGF, and collagen are highly expressed in human CRSsNP nasal mucosa specimens, suggesting their roles in tissue remodeling during CRSsNP progression. |
| 關聯: | Journal of Cellular Physiology, v.234, n.7, pp.10489-10499 |
| 顯示於類別: | [休閒保健管理系(所)] 期刊論文
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