TGF-beta 1-induced HSP47 regulates extracellular matrix accumulation via Smad2/3 signaling pathways in nasal fibroblasts
- Authors
- Kim, Hae-Ji; Park, Joo-Hoo; Shin, Jae Min; Yang, Hyun-Woo; Lee, Heung Man; Park, Il-Ho
- Issue Date
- Oct-2019
- Publisher
- Nature Publishing Group
- Citation
- Scientific Reports, v.9, no.1
- Indexed
- SCI
SCIE
SCOPUS
- Journal Title
- Scientific Reports
- Volume
- 9
- Number
- 1
- URI
- https://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/1504
- DOI
- 10.1038/s41598-019-52064-1
- ISSN
- 2045-2322
- Abstract
- 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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Collections - 4. Research institute > Institute for Medical Device Clinical Trial > 1. Journal Articles
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