GPR68 Senses Flow and Is Essential for Vascular Physiology
In: Cell, Jg. 173 (2018-04-01), Heft 3
Online
academicJournal
- 762 - 775.e16
Mechanotransduction plays a crucial role in vascular biology. One example of this is the local regulation of vascular resistance via flow-mediated dilation (FMD). Impairment of this process is a hallmark of endothelial dysfunction and a precursor to a wide array of vascular diseases, such as hypertension and atherosclerosis. Yet the molecules responsible for sensing flow (shear stress) within endothelial cells remain largely unknown. We designed a 384-well screening system that applies shear stress on cultured cells. We identified a mechanosensitive cell line that exhibits shear stress-activated calcium transients, screened a focused RNAi library, and identified GPR68 as necessary and sufficient for shear stress responses. GPR68 is expressed in endothelial cells of small-diameter (resistance) arteries. Importantly, Gpr68-deficient mice display markedly impaired acute FMD and chronic flow-mediated outward remodeling in mesenteric arterioles. Therefore, GPR68 is an essential flow sensor in arteriolar endothelium and is a critical signaling component in cardiovascular pathophysiology.
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GPR68 Senses Flow and Is Essential for Vascular Physiology
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Autor/in / Beteiligte Person: | Xu, Jie ; Mathur, Jayanti ; Vessières, Emilie ; Hammack, Scott ; Nonomura, Keiko ; Favre, Julie ; Grimaud, Linda ; Petrus, Matt ; Francisco, Allain ; Li, Jingyuan ; Lee, Van ; Xiang, Fu-li ; Mainquist, James K ; Cahalan, Stuart M ; Orth, Anthony P ; Walker, John R ; Ma, Shang ; Lukacs, Viktor ; Bordone, Laura ; Bandell, Michael ; Laffitte, Bryan ; Xu, Yan ; Chien, Shu ; Henrion, Daniel ; Patapoutian, Ardem |
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Zeitschrift: | Cell, Jg. 173 (2018-04-01), Heft 3 |
Veröffentlichung: | eScholarship, University of California, 2018 |
Medientyp: | academicJournal |
Umfang: | 762 - 775.e16 |
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