Department of Otorhinolaryngology-Head and Neck Surgery, Korea University College of Medicine, Seoul 08308, Korea.
Upper Airway Chronic Inflammatory Diseases Laboratory, Korea University College of Medicine, Seoul 08308, Korea.
Int J Mol Sci. 2021 Oct 26;22(21):11535. doi: 10.3390/ijms222111535.
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 and heat shock protein 47 (HSP47) may be engaged in the pathophysiology of CRS. This study aimed to determine the role of and HSP47 in modulating transforming growth factor (TGF)-β1-induced EMT and migration in airway epithelial cells. Expression levels of , HSP47, E-cadherin, α-smooth muscle actin (α-SMA), vimentin and fibronectin were assessed through real-time PCR, Western blotting, and immunofluorescence staining. () targeted against and were transfected to regulate the expression of EMT-related markers. Cell migration was evaluated with wound scratch and transwell migration assay. mimic significantly inhibited the expression of HSP47 and TGF-β1-induced EMT-related markers in A549 cells. However, the 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 and HSP47 in A549 cells. These findings were further verified in primary nasal epithelial cells. 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 and HSP47 in pathologic tissue remodeling progression in CRS.
组织重塑导致慢性鼻-鼻窦炎（CRS）的持续炎症和难治性。在这个过程中，上皮-间充质转化（EMT）在失调的重塑中起着重要作用， 和热休克蛋白 47（HSP47）可能参与 CRS 的病理生理学。本研究旨在确定 在调节气道上皮细胞中转化生长因子（TGF）-β1诱导的 EMT 和迁移中的作用。通过实时 PCR、Western blot 和免疫荧光染色评估 、HSP47、E-钙黏蛋白、α-平滑肌肌动蛋白（α-SMA）、波形蛋白和纤维连接蛋白的表达水平。 针对 和 的 siRNA 转染用于调节 EMT 相关标志物的表达。通过划痕实验和 Transwell 迁移实验评估细胞迁移。 模拟物显著抑制 A549 细胞中 HSP47 和 TGF-β1 诱导的 EMT 相关标志物的表达。然而， 抑制剂更能诱导它们的表达。HSP47 敲除抑制 TGF-β1 诱导的 EMT 标志物水平。功能研究表明，TGF-β1 诱导的 EMT 是通过 A549 细胞中的 和 HSP47 调节的。这些发现进一步在原代鼻上皮细胞中得到验证。 在 A549 和原代鼻上皮细胞中通过 HSP47 表达调节调节 TGF-β1 诱导的 EMT 相关标志物和迁移。这些结果表明 在 CRS 病理性组织重塑进展中的重要性。
