期刊
CIRCULATION RESEARCH
卷 92, 期 12, 页码 1296-1304出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/01.RES.0000078780.65824.8B
关键词
mechanotransduction; endothelial cells; sterol regulatory element binding proteins; shear stress; Rho
资金
- NHLBI NIH HHS [HL64382, HL60789, HL19454] Funding Source: Medline
Previous studies have shown that integrin activation and fluid shear stress can modulate the activity of sterol regulatory element binding proteins (SREBPs) in vascular endothelial cells. We investigated the role of small GTPase Rho-mediated signal transduction pathway in this mode of SREBP activation. Fluid shear stress activates the Rho downstream effectors ROCK, LIM kinase (LIMK), and cofilin. The various negative mutants of RhoA, ROCK, LIMK, and cofilin can block the shear stress activation of SREBPs. The shear stress-activated SREBP depends on S2P proteases but not caspase-3. Mechanistically, the endoplasmic reticulum-to-Golgi transport of SREBP cleavage activating protein requires the actin-based cytoskeleton and is enhanced by the Rho-ROCK-LIMK-cofilin pathway. By enhancing the SREBP-mediated cholesterol metabolism, this unique mechanism may contribute to endothelial cell functions under flow.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据