miR-29b Regulates TGF-β1-Induced Epithelial–Mesenchymal Transition by Inhibiting Heat Shock Protein 47 Expression in Airway Epithelial Cells

Abstract

Tissue remodeling contributes to ongoing inflammation and refractoriness of chronic rhinosinusitis (CRS). During this process, epithelial-mesenchymal transition (EMT) plays an important role in dysregulated remodeling and both microRNA (miR)-29b and heat shock protein 47 (HSP47) may be engaged in the pathophysiology of CRS. This study aimed to determine the role of miR-29b and HSP47 in modulating transforming growth factor (TGF)-β1-induced EMT and migration in airway epithelial cells. Expression levels of miR-29b, HSP47, E-cadherin, α-smooth muscle actin (α-SMA), vimentin and fibronectin were assessed through real-time PCR, Western blotting, and immunofluorescence staining. Small interfering RNA (siRNA) targeted against miR-29b and HSP47 were transfected to regulate the expression of EMT-related markers. Cell migration was evaluated with wound scratch and transwell migration assay. miR-29b mimic significantly inhibited the expression of HSP47 and TGF-β1-induced EMT-related markers in A549 cells. However, the miR-29b inhibitor more greatly induced the expression of them. HSP47 knockout suppressed TGF-β1-induced EMT marker levels. Functional studies indicated that TGF-β1-induced EMT was regulated by miR-29b and HSP47 in A549 cells. These findings were further verified in primary nasal epithelial cells. miR-29b modulated TGF-β1-induced EMT-related markers and migration via HSP47 expression modulation in A549 and primary nasal epithelial cells. These results suggested the importance of miR-29b and HSP47 in pathologic tissue remodeling progression in CRS.

NLRP3 participates in IL-17A-induced epithelial-mesenchymal transition in human nasal epithelial cells of chronic rhinosinusitis with nasal polyps

“…Besides, due to deposition of various matrix proteins, the basement membrane of the submucosa is eventually thickened [3] . The role of EMT in the pathogenesis of airway diseases has been extensively investigated [24][25][26] and EMT has been shown to be one of the mechanisms implicated to pathologic tissue remodeling in CRSwNP [27][28][29] .…”

Targeting HSP47 for cancer treatment

“…As a primary factor that drives fibrosis and tumorigenesis, TGF-β1 can upregulate HSP47 expression via Smad2/3 signaling pathway in nasal fibroblasts [151,152]. The cytokine IL-1β is a key mediator of the inflammatory response and could regulate fibrosis and tumor progression [153].…”