酸3-酶调节的细胞成熟控制了血管重塑
Ana M Figueiredo1, Pilar Villacampa1, Rodrigo Diéguez-Hurtado2
1Vascular Biology and Signalling Group, ProCURE, Oncobell Program, Institut d´Investigació Biomèdica de Bellvitge (IDIBELL), Gran Via de l'Hospitalet 199, 08908 L´Hospitalet de Llobregat, Barcelona, Spain (A.M.F., P.V., P.K., A.M.-R., A.A.-U., M.G.).
Circulation
|May 30, 2020
概括
酸3-酶β (PI3Kβ) 的活性控制了血管形成过程中的细胞成熟. 抑制PI3Kβ加速细胞周成熟,这对于适当的血管生成至关重要,并可能提供新的治疗点.
科学领域:
- 血管生物学
- 细胞信号传输
- 发育生物学
背景情况:
- 细胞对于血管的稳定和功能至关重要.
- 细胞损失与糖尿病视网膜病变和癌症等疾病有关.
- 血管新生过程中的细胞周细胞的分子调节还不清楚.
研究的目的:
- 在血管生成过程中研究细胞细胞的转录程序.
- 阐明酸3-激酶 (PI3K) 在细胞周围生物中的信号传递作用.
- 了解血管形成过程中细胞成熟的调节.
主要方法:
- 使用基因小鼠模型 (Pdgfrb-CreER x RiboTag) 进行细胞转录学.
- 使用R26-mTmG记者小鼠进行单细胞标签的评估.
- 使用基因模型在壁细胞中禁用PI3Kα,PI3Kβ和PTEN.
主要成果:
- 在血管新生开始时,细胞表现出增殖和激活PI3K信号,在重塑过程中转移到成熟功能,PI3K信号减少.
- PI3Kβ,而不是PI3Kα,调节细胞增殖和成熟;PI3Kβ无活化加速成熟.
- 删除PTEN (增强PI3K信号传递) 延迟细胞成熟,这对于血管重塑至关重要.
结论:
- 鉴定出新型细胞成熟的分子和形态标志物.
- PI3Kβ活动作为适当的血管形成的关键检查点.
- 这些发现表明针对PI3Kβ的潜在治疗策略可以调节疾病中的血管生成.
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