| First Author | Xu J | Year | 2018 |
| Journal | Cell | Volume | 173 |
| Issue | 3 | Pages | 762-775.e16 |
| PubMed ID | 29677517 | Mgi Jnum | J:261127 |
| Mgi Id | MGI:6153469 | Doi | 10.1016/j.cell.2018.03.076 |
| Citation | Xu J, et al. (2018) GPR68 Senses Flow and Is Essential for Vascular Physiology. Cell 173(3):762-775.e16 |
| abstractText | 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. |
