Abstract
Background: Airway remodeling is one of the reasons for severe steroidresistant asthma related to HMGB1/RAGE signaling or Th17 immunity.
Objective: Our study aims to investigate the relationship between the HMGB1/RAGE signaling and the Th17/IL-17 signaling in epithelial-mesenchymal transformation (EMT) of airway remodeling.
Methods: CD4+ T lymphocytes were collected from C57 mice. CD4+ T cell and Th17 cell ratio was analyzed by flow cytometry. IL-17 level was detected by ELISA. The Ecadherin and α-SMA were analyzed by RT-qPCR and immunohistochemistry. The Ecadherin, α-SMA, and p-Smad3 expression were analyzed by western blot.
Results: The HMGB1/RAGE signaling promoted the differentiation and maturation of Th17 cells in a dose-dependent manner in vitro. The HMGB1/RAGE signaling also promoted the occurrence of bronchial EMT. The EMT of bronchial epithelial cells was promoted by Th17/IL-17 and the HMGB1 treatment in a synergic manner. Silencing of RAGE reduced the signaling transduction of HMGB1 and progression of bronchial EMT.
Conclusion: HMGB1/RAGE signaling synergistically enhanced TGF-β1-induced bronchial EMT by promoting the differentiation of Th17 cells and the secretion of IL-17.
Keywords: HMGB1, RAGE, Th17/IL-17, EMT, airway remodeling, bronchial asthma
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