感应pH的GPR68通过Rap1A抑制了血管光滑肌肉细胞的增殖
Madison D Williams1, Joshua S Morgan1, Michael T Bullock1
1Department of Physiology, Brody School of Medicine, East Carolina University, Greenville, North Carolina, United States.
American journal of physiology. Heart and circulatory physiology
|September 13, 2024
概括
感应pH的GPR68受体抑制了血管光滑肌肉细胞的生长. GPR68的丧失促进了由小GTPase Rap1A调解的增殖,为心血管疾病提供了潜在的治疗点.
科学领域:
- 心血管生物学 心血管生物学
- 细胞的新陈代谢
- 分子医学是分子医学.
背景情况:
- 血管光滑肌 (VSM) 细胞的表型转变是心血管疾病 (CVD) 的核心.
- 由于新陈代谢改变而引起的组织酸性是心血管疾病的一个特征,但它在VSM病理中的作用尚未得到研究.
- 感应pH的G蛋白结合受体GPR68在VSM中的作用基本上是未知的.
研究的目的:
- 调查GPR68对体内和体外VSM增殖的监管影响.
- 阐明GPR68对VSM生长影响的分子机制.
- 探索GPR68及其效应因子作为心血管疾病的潜在治疗点.
主要方法:
- 使用野生型 (WT) 和GPR68淘汰赛 (KO) 的雄性和雌性小鼠进行体内和体外研究.
- 评估VSM增殖和细胞循环进展,以应对动脉损伤和酸性条件.
- 使用RNA沉默分析了包括Rap1A在内的关键信号分子的mRNA和蛋白质表达.
主要成果:
- 动脉损伤减少了WT血管中的GPR68表达,并加剧了GPR68KO血管中的重塑.
- 与WT细胞相比,GPR68 KO VSM细胞表现出增加的增殖.
- 酸性暴露减少了WT VSM细胞的增殖,而GPR68缺乏导致Rap1A表达的增加,从而推动了增殖.
结论:
- 感应pH的GPR68在VSM中具有增长抑制能力.
- 小型GTPase Rap1A是GPR68控制的VSM生长的关键媒介.
- GPR68和Rap1A代表了预防心血管疾病病理性VSM增殖的潜在治疗点.
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