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  • Title: HMGB1/RAGE Signaling Regulates Th17/IL-17 and Its Role in Bronchial Epithelial-Mesenchymal Transformation.
    Author: Sun J, Jiang Y, Li L, Li R, Ling F, Du X, Han Q, Chu S, Liang Y, Mai L, Ma L.
    Journal: Curr Mol Med; 2024; 24(11):1401-1412. PubMed ID: 37921188.
    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.
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