HMGB1/RAGE Signaling Regulates Th17/IL-17 and Its Role in Bronchial Epithelial-Mesenchymal Transformation.

Abstract

Airway remodeling is one of the reasons for severe steroidresistant asthma related to HMGB1/RAGE signaling or Th17 immunity. 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. 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. 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. HMGB1/RAGE signaling synergistically enhanced TGF-β1-induced bronchial EMT by promoting the differentiation of Th17 cells and the secretion of IL-17.