TRPC4通过促进肺内皮细胞亡来加剧缺氧性肺高血压
Liu Yang1, Zeyu Peng1, Fanpeng Gong1
1Wuxi School of Medicine, Jiangnan University, Wuxi, China.
Free radical biology & medicine
|April 18, 2024
概括
肺动脉内皮细胞中的TRPC4通道通过增加细胞亡和血管重塑来促进肺高血压. 抑制TRPC4为治疗这种疾病提供了潜在的治疗策略.
科学领域:
- 心血管生物学 心血管生物学
- 细胞生理学 细胞生理学
- 分子医学是分子医学.
背景情况:
- 肺高血压 (PH) 是一种严重的疾病,治疗方法有限,其特点是肺血管重塑.
- 肺动脉内皮细胞 (PAEC) 功能障碍是PH病变的核心.
- 规范性短暂受体潜能 (TRPC) 通道与各种疾病有关,但它们在PH中的作用需要进一步阐明.
研究的目的:
- 研究PAEC中TRPC4通道在PH发展中的作用.
- 阐明TRPC4影响PH进展的分子机制.
主要方法:
- 从PH模型 (低氧/SU5416,单色素) 的PAEC和暴露于低氧的PAEC中分析了TRPC4表达.
- 使用腺相关病毒 (AAV) 血清型6或用TRPC4抗剂抑制TRPC4的沉默.
- 评估了PAEC亡,内细胞网膜应激 (ERS),反应性氧物种 (ROS) 和基因表达 (RNA测序).
主要成果:
- 在PH模型和暴露于缺氧的PAEC中,TRPC4表达被上调.
- TRPC4的淘汰或抑制降低了PH的严重程度,PAEC的亡,ERS和ROS的产生.
- TRPC4缺乏抑制了含有2 (Susd2) 表达的亲细胞突变蛋白寿司域,而TRPC4促进了Susd2介导的PAEC亡.
结论:
- 在PAEC中,TRPC4通道通过通过caspase-12/ERS通路促进细胞灭绝并增加Susd2表达,从而加剧PH.
- 抑制TRPC4可以改善PH和PAEC的亡,这表明TRPC4和Susd2信号是PH的潜在治疗标.
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