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TGFβ mediates collagen production in human CRSsNP nasal mucosa‐derived fibroblasts through Smad2/3‐dependent pathway and CTGF induction and secretion
Author(s) -
Shieh JiunnMin,
Tsai YihJeng,
Chi Jessie ChaoYun,
Wu WenBin
Publication year - 2019
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.27718
Subject(s) - ctgf , transforming growth factor , extracellular matrix , microbiology and biotechnology , connective tissue , gene knockdown , growth factor , fibrosis , transforming growth factor beta , secretion , small interfering rna , biology , fibroblast , chemistry , endocrinology , medicine , cell culture , rna , biochemistry , receptor , gene , genetics
Chronic rhinosinusitis without nasal polyp (CRSsNP) is characterized by tissue remodeling and fibrosis. Transforming growth factor‐β (TGF‐β) 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‐β1 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‐β1 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‐β1 and its isoforms could promote collagen protein expression. Concomitantly, TGF‐β1 caused CTGF expression and secretion. An addition of exogenous CTGF to fibroblasts also caused collagen expression. In accordance with these observations, TGF‐β1, CTGF, and collagen were highly expressed in the subepithelial stroma region of CRSsNP nasal mucosa, as determined by immunohistochemistry. The TGF‐β1‐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‐β1‐mediated collagen expression. Collectively, our results provide first and further evidence that TGF‐β1 mediates collagen expression–production through a canonical Smad2/3‐dependent pathway and CTGF induction and secretion in human nasal fibroblasts. Moreover, TGF‐β1, CTGF, and collagen are highly expressed in human CRSsNP nasal mucosa specimens, suggesting their roles in tissue remodeling during CRSsNP progression.