揭示了使用人类尿液衍生的细胞诱导的 ангиотензин II 和 洛萨坦基因调节网络
Chantelle Thimm1, Lars Erichsen1, Wasco Wruck1
1Institute for Stem Cell Research and Regenerative Medicine, Medical Faculty, Heinrich-Heine University Düsseldorf, 40225 Düsseldorf, Germany.
International journal of molecular sciences
|July 14, 2023
概括
研究人员将尿液衍生的原体细胞分化为 podocytes. 这些细胞模拟了 ангиотензинII和洛萨坦如何影响宁- ангиотензин-阿尔多斯特系统 (RAAS),有助于病研究.
科学领域:
- 腎臟病學 (nephrology) 是一種醫學專業.
- 再生医学是一种再生医学.
- 分子生物学分子生物学
背景情况:
- 细胞对于脏过至关重要;它们的损伤导致脏疾病.
- 高血压涉及氨酸- ангиотензин- алдостерон系统 (RAAS),其中 ангиотензин II (ANG II) 调解细胞亡.
- 洛萨坦是一种血管激素II型I受体 (AGTR1) 阻断剂,通过调节RAAS,用于治疗高血压.
研究的目的:
- 为了将SIX2-阳性尿源原体细胞 (UdRPCs) 分化为成熟的 podocytes.
- 为了研究ANG II和洛萨坦对RAAS在分化细胞中的信号传递的影响.
- 分析洛萨坦和ANG II联合刺激引起的基因表达变化.
主要方法:
- 区分 UdRPC 和 UM51-hTERT 细胞成成熟的 podocytes.
- 用 ANG II 和洛萨坦激活分化细胞.
- 对 ангиотензин-II 受体表达的分析 (AGTR1 和 AGTR2).
- 转录组分析以确定差异表达的基因.
主要成果:
- 不同化的小细胞表现出 ANG II 相关的 RAAS 激活,上调 AGTR1 和下调 AGTR2.
- 洛萨坦治疗抵消了ANG II效应,有利于AGTR2而不是AGTR1.
- 转录组分析确定了洛萨坦和共同刺激影响的关键基因和途径,包括与血管功能,DNA甲基化和细胞分化相关的基因和途径.
结论:
- 从 UdRPC 衍生出的 podocytes 作为一个有价值的模型来研究 RAAS 途径激活和调节在脏疾病.
- 该模型促进了对毒性和针对RAAS的潜在治疗策略的研究.
- 这些发现提供了对洛萨坦对细胞的影响背后的分子机制的见解.
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