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- Molecular Biology
- Molecular Medicine
- General Medicine
- Biochemistry
background:
Airway remodeling is one of the reasons for severe steroid-resistant asthma, which was 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 EMT of airway remodeling.
method:
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 E-cadherin and α-SMA was analyzed by RT-qPCR and immunohistochemistry. The E-cadherin, α-SMA, and p-Smad3 expression was analyzed by western blot.
result:
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 enhanced the process of bronchial EMT by promoting the differentiation of Th17 cells and the secretion of IL-17.