通过抑制EndMT和改善内皮屏障功能,S1PR1减轻了肺纤维化
Wenfang Xiong1, Shuhua Chen2, Hong Xiang3
1Health Management Center, the Third Xiangya Hospital of Central South University, Changsha, Hunan, 410013, PR China; Department of Cardiology, the Third Xiangya Hospital of Central South University, Changsha, Hunan, 410013, PR China.
Pulmonary pharmacology & therapeutics
|June 9, 2023
概括
素1-酸盐受体1 (S1PR1) 通过防止内皮细胞-介质细胞转化 (EndMT) 和屏障损伤,保护肺纤维化. 准S1PR1可能为异形性肺纤维化 (IPF) 提供一种新的治疗策略.
科学领域:
- 肺部医学 肺部医学
- 细胞生物学 细胞生物学
- 纤维化研究 纤维化研究
背景情况:
- 异形性肺纤维化 (IPF) 是一种致命的肺病,其特征是纤维细胞增殖和细胞外基质沉积.
- 内皮细胞-介质细胞转化 (EndMT) 是IPF中产生纤维细胞的新发现的机制,但其精确的调节尚不清楚.
- 在EndMT驱动的肺纤维化中,斯芬戈-1-酸盐受体1 (S1PR1) 的作用需要研究.
研究的目的:
- 为了研究氨酸1-酸盐受体1 (S1PR1) 在内皮细胞-介质细胞转化 (EndMT) 和肺纤维化中的作用.
- 确定S1PR1调制是否影响EndMT,内皮屏障完整性以及肺纤维化模型中的相关信号通路.
主要方法:
- 在C57BL/6小鼠中使用白色素 (BLM) 诱导肺纤维化,并在肺微血管内皮细胞中使用TGF-β1.1.
- 分析了S1PR1的表达,使用西方斑点,流细胞计和免疫光.
- 在实验室和体内使用S1PR1激动剂和抗剂来评估它们对EndMT,内皮屏障功能和信号通路 (Smad2/3,RhoA/ROCK1) 的影响.
主要成果:
- 在肺纤维化实验室和实验室活体模型中,内皮S1PR1蛋白表达显著下调.
- 减少S1PR1表达促进了EndMT,由改变的内皮和介质细胞标记物表达和内皮屏障破坏证明.
- 刺激S1PR1抑制了TGF-β1诱导的Smad2/3和RhoA/ROCK1通路的激活,从而保护了内皮屏障.
结论:
- 内皮质S1PR1通过抑制EndMT和减轻内皮质屏障损伤,在肺纤维化中起着保护作用.
- S1PR1代表了管理渐进性异常性肺纤维化 (IPF) 的潜在治疗标.
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