高迁移率族蛋白 B1/晚期糖基化终末产物受体信号通路调控 Th17/IL-17 及其在支气管上皮-间充质转化中的作用。

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

机构信息

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

出版信息

Curr Mol Med. 2024;24(11):1401-1412. doi: 10.2174/0115665240249953231024060610.

DOI:10.2174/0115665240249953231024060610

PMID: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.

摘要

背景

气道重塑是与 HMGB1/RAGE 信号或 Th17 免疫相关的严重类固醇抵抗性哮喘的原因之一。

目的

本研究旨在探讨 HMGB1/RAGE 信号与上皮间质转化（EMT）中 Th17/IL-17 信号在气道重塑中的关系。

方法

从 C57 小鼠中收集 CD4 T 淋巴细胞。通过流式细胞术分析 CD4 T 细胞和 Th17 细胞的比例。通过 ELISA 检测 IL-17 水平。通过 RT-qPCR 和免疫组织化学分析 Ecadherin 和 α-SMA。通过 Western blot 分析 Ecadherin、α-SMA 和 p-Smad3 的表达。