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

Jingyi Sun; Yan Jiang; Linqiao Li; Rou Li; Feixiang Ling; Xiaojing Du; Qian Han; Shuyuan Chu; Yaxi Liang; Lin Mai; Libing Ma

doi:10.2174/0115665240249953231024060610

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

Curr Mol Med. 2023 Oct 27. doi: 10.2174/0115665240249953231024060610. Online ahead of print.

Authors

Jingyi Sun¹, Yan Jiang¹, Linqiao Li¹, Rou Li¹, Feixiang Ling¹, Xiaojing Du¹, Qian Han¹, Shuyuan Chu¹, Yaxi Liang¹, Lin Mai¹, Libing Ma¹

Affiliation

¹ Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, 541001, China.

PMID: 37921188
DOI: 10.2174/0115665240249953231024060610

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: EMT; HMGB1; RAGE; Th17/IL-17; airway remodeling; bronchial asthma.