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.
Highlights
Chronic rhinosinusitis (CRS) is defined as the persistent inflammation of the sinonasal mucosa and is a very heterogeneous disorder with unclear pathophysiology that lasts for over 12 weeks [1]
To evaluate the effect of transforming growth factor (TGF)-β1 on miR-29b and heat shock protein 47 (HSP47) expression in A549 cells, we measured miR-29b and HSP47 mRNA expression using quantitative real-time PCR in A549 cells treated with TGF-β1 at the indicated doses (0.5, 1, 2.5, 5 or 10 ng/mL, 24 h)
These results indicated that HSP47, a direct target of miR-29b, was induced by TGF-β1 in A549 cells
Summary
Chronic rhinosinusitis (CRS) is defined as the persistent inflammation of the sinonasal mucosa and is a very heterogeneous disorder with unclear pathophysiology that lasts for over 12 weeks [1]. The majority of CRS patients who fail optimal standard medical treatment are candidates for surgery. 10–20% of patients with CRS show only slight improvement in symptoms despite medical and surgical therapy, which is considered refractory CRS [2]. Recent studies suggest that the damage to the physical barrier in the sinonasal epithelium by exogenous agents leads to a dysregulated immune response and pathologic remodeling contributing to disease recalcitrance in CRS [3,4]. Tissue remodeling is a core reaction to stress, such as damage to tissues or chronic inflammation. It is well known that in the lower airway diseases, such as asthma or chronic obstructive pulmonary disease, the upper airway diseases, such as allergic rhinitis or CRS are associated with tissue remodeling [5]
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