激活GPR39通过抑制ETS-1介导的VEGF-A/VEGFR2信号,减轻AngII诱导的腹腔大动脉动脉瘤
Bin Liu1,2, Yiming Xu3, Yuanyuan Liu4
1Department of Vascular Surgery, The First Clinical College of Shandong University of Traditional Chinese Medicine, Ji'nan City, Shandong, China.
Clinical and experimental pharmacology & physiology
|June 30, 2025
概括
使用TC-G 1008激活G蛋白结合受体39 (GPR39) 通过减少氧化应激和抑制血管生成,可以防止腹腔大动脉动脉瘤 (AAA). 这项研究揭示了GPR39的存在.
科学领域:
- 血管生物学和医学 血管生物学和医学
- 分子和细胞生物学分子和细胞生物学
- 药理学和治疗学 药理学和治疗学
背景情况:
- 腹腔大动脉动脉瘤 (AAA) 是一种危及生命的血管疾病,其特征是大动脉壁衰弱和扩张.
- 氧化应激和血管生成是AAA发展中的关键病原性过程.
- 在AAA病变发生过程中,G蛋白结合受体39 (GPR39) 的作用在很大程度上仍未被探索.
研究的目的:
- 在ApoE-/-小鼠中研究G蛋白结合受体39 (GPR39) 在血管素II (AngII) 诱导的腹腔大动脉动脉瘤 (AAA) 中的功能.
- 阐明GPR39影响AAA进展的潜在分子机制.
- 评估GPR39激活在缓解AAA方面的治疗潜力.
主要方法:
- 在ApoE-/-小鼠中输注 ангиотензинII (AngII) 诱导AAA.
- 在体内和体内测试,包括组织学分析,ELISA,西式涂抹,定量PCR和血管管形成测试.
- 用GPR39激动剂TC-G 1008来评估其对AAA进展和分子通路的影响.
主要成果:
- 在AAA组织中,GPR39的表达显著下调.
- TC-G 1008治疗减轻了AAA的进展,减少了动脉瘤发生率和大小,减轻了氧化应激,并抑制了VEGF-A/VEGFR2表达.
- 在体外,TC-G 1008通过通过ETS-1转录因子向下调节VEGF-A/VEGFR2信号来抑制血管生成.
结论:
- 通过TC-G 1008激活GPR39,表明对AngII诱导的AAA产生保护作用.
- 该机制涉及减轻氧化应激和通过VEGF-A/VEGFR2通路抑制ETS-1介导的血管生成.
- 激活GPR39代表了治疗腹腔大动脉动脉瘤的潜在治疗策略.
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