维生素D受体及其在人类肺动脉高血压中的抗增殖作用
Maria Callejo1,2, Daniel Morales-Cano1,2,3, Miguel A Olivencia1,2,3
1Department of Pharmacology and Toxicology, Facultad de Medicina, School of Medicine, Universidad Complutense de Madrid, Pza Ramón y Cajal s/n., 28040, Madrid, Spain.
维生素D缺乏症在肺动脉高血压 (PAH) 中很常见. 这项研究表明,卡尔西醇对维生素D受体 (VDR) 的激活通过影响生存和BMP通路来减少PAH细胞中的增殖.
科学领域:
- 心血管研究研究心血管研究
- 内分泌学 在内分泌学.
- 分子生物学分子生物学
背景情况:
- 维生素D (vitD) 缺乏在肺动脉高血压 (PAH) 患者中很普遍,与较差的结果相关.
- 维生素D受体 (VDR) 和其在PAH患者人肺血管中的信号通路的作用仍未得到充分研究.
研究的目的:
- 研究VDR表达及其在PAH患者肺血管中的抗增殖功能.
- 分析肺动脉光滑肌细胞 (PASMC) 和内皮细胞 (PAEC) 中的VDR信号通路.
主要方法:
- 从对照组和PAH患者的肺组织,PASMC和PAEC中分析了VDR表达.
- 接受PASMC治疗的卡尔西醇检查了VDR和VDR标基因表达 (KCNK3,BIRC5,BMP4).
- 使用MTT和BrdU试验评估了利醇的抗增殖作用,其中包括向基因沉默/抑制.
主要成果:
- 与对照组相比,PAH患者的VDR表达在肺部和PASMC下调,但在PAEC中没有.
- 在PASMC中,酸盐治疗显著提高了VDR表达和基因 (KCNK3,BIRC5,BMP4) 的调节.
- 酸在PASMC中表现出抗增殖作用,这取决于幸存者和BMPR2,但不是TASK1.1.
结论:
- 在PAH中,VDR表达减少,但可以通过酸恢复.
- VDR激活在PASMC中具有抗增殖作用,通过生存素和BMP信号通路进行介导.
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