Title:HMGB1/RAGE Signaling Regulates Th17/IL-17 and Its Role in Bronchial Epithelial-Mesenchymal Transformation
Volume: 24
Issue: 11
关键词:
HMGB1, RAGE, Th17/IL-17, EMT,气道重塑,支气管哮喘。
摘要:
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.