MAPK/ERK通路
每2
每1
血管紧张素II
血管平滑肌
细胞生物学
生物
信号转导
蛋白激酶A
下调和上调
基因沉默
细胞周期
细胞生长
激酶
内分泌学
内科学
生物钟
时钟
细胞
昼夜节律
生物化学
医学
基因
血压
平滑肌
作者
Wan Jin,Yu Tian,Yanyun Ding,Deixi Zhou,Long Li,Meng Yuan,Yuanzhu Wu,Mingqi Ye,Jiajie Luan,Kui Yang
出处
期刊:PubMed
日期:2023-06-20
卷期号:: 1-15
标识
DOI:10.1080/07420528.2023.2224904
摘要
The circadian rhythm of blood pressure (BP) is believed to be regulated by the clock system, which is closely linked to levels of angiotensin II (Ang II). This study aimed to investigate whether Ang II mediates the proliferation of vascular smooth muscle cells (VSMCs) through the interaction between the clock system and the mitogen-activated protein kinase (MAPK) signaling pathway. Primary rat aortic VSMCs were treated with Ang II, with or without MAPK inhibitors. VSMC proliferation, expression of clock genes, CYCLIN E, and MAPK pathways were assessed. Ang II treatment resulted in increased VSMC proliferation and rapid upregulation of clock gene Periods (Pers) expression. Compared to the non-diseased control (NC) group, VSMCs incubated with Ang II displayed a noticeable delay in the G1/S phase transition and downregulation of CYCLIN E upon silencing of Per1 and Per2 genes. Importantly, silencing Per1 or Per2 in VSMCs led to decreased expression of key MAPK pathway proteins, including RAS, phosphorylated mitogen-activated protein kinase (P-MEK), and phosphorylated extracellular signal-regulated protein kinase (P-ERK). Moreover, the MEK and ERK inhibitors, U0126 and SCH772986, significantly attenuated the Ang II-induced proliferation of VSMCs, as evidenced by an increased G1/S phase transition and decreased CYCLIN E expression. The MAPK pathway plays a critical role in regulating VSMC proliferation in response to Ang II stimulation. This regulation is controlled by the expression of circadian clock genes involved in the cell cycle. These findings provide novel insights for further research on diseases associated with abnormal VSMC proliferation.
科研通智能强力驱动
Strongly Powered by AbleSci AI