TGF-β1-induced HSP47 regulates extracellular matrix accumulation via Smad2/3 signaling pathways in nasal fibroblasts

被引：27
作者：
Kim, Hae-Ji [1 ]
Park, Joo-Hoo [1 ,2 ,4 ]
Shin, Jae-Min [1 ,2 ,4 ]
Yang, Hyun-Woo [1 ,4 ]
Lee, Heung-Man [1 ,2 ,4 ]
Park, Il-Ho [1 ,2 ,3 ,4 ]
机构：
[1] Korea Univ, Coll Med, Upper Airway Chron Inflammatory Dis Lab, Seoul, South Korea
[2] Korea Univ, Coll Med, Med Devices Clin Trials Lab, Seoul, South Korea
[3] Korea Univ, IVD Support Ctr, Coll Med, Seoul, South Korea
[4] Korea Univ, Dept Otorhinolaryngol Head & Neck Surg, Coll Med, Seoul, South Korea
来源：
SCIENTIFIC REPORTS | 2019年 / 9卷 / 1期
关键词：
CHRONIC RHINOSINUSITIS; MOLECULAR CHAPERONE; PIRFENIDONE; REPAIR;
D O I：
10.1038/s41598-019-52064-1
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
HSP47 is required for the production of collagen and serves an important role in tissue remodeling, a pathophysiologic mechanism of chronic rhinosinusitis (CRS). We investigated the relationship between HSP47 expression and tissue remodeling in CRS. We also determined the underlying molecular mechanisms of TGF-beta 1-induced HSP47 and extracellular matrix (ECM) production in nasal fibroblasts. HSP47, alpha-SMA, fibronectin, and collagen type I expression levels were measured using real-time PCR, western blotting, and immunofluorescence staining. Fibroblast migration was analyzed using scratch and transwell migration assays. Contractile activity was measured with a collagen gel contraction assay. HSP47 is increased in patients with CRS without nasal polyps. TGF-beta 1 induced HSP47 expression in nasal fibroblasts. Myofibroblast differentiation and ECM production, which are induced by TGF-beta 1, were inhibited by siHSP47. We also confirmed that the Smad2/3 signaling pathway is involved in TGF-beta 1-induced HSP47 expression in nasal fibroblasts. In a functional assay, TGF-beta 1-enhanced migration and contraction ability were inhibited by HSP47 knockout. Glucocorticoid reversed the stimulatory effects of TGF-beta 1 on HSP47 expression and ECM production in nasal fibroblasts and ex vivo organ cultures. HSP47 expression is involved in TGF-beta 1-induced myofibroblast differentiation and ECM production through the Smad2/3 signaling pathway, which might contribute to tissue remodeling in chronic rhinosinusitis.
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页数：11
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