GPR68 Senses Flow and Is Essential for Vascular Physiology
| Autor: | Bryan A. Laffitte, Jingyuan Li, Matt Petrus, Linda Grimaud, Keiko Nonomura, James Kevin Mainquist, Stuart M. Cahalan, Jayanti Mathur, Van Lee, Emilie Vessières, Yan Xu, Fu-Li Xiang, Julie Favre, Ardem Patapoutian, Daniel Henrion, Jie Xu, Laura Bordone, Anthony P. Orth, Allain G. Francisco, Shu Chien, Shang Ma, Viktor Lukacs, Scott Hammack, John R. Walker, Michael Bandell |
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| Přispěvatelé: | Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA) |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Mechanotransduction Vasodilation Biocompatible Materials outward remodeling Inbred C57BL Cardiovascular Mechanotransduction Cellular Medical and Health Sciences Receptors G-Protein-Coupled Mice GPCR immune system diseases hemic and lymphatic diseases Receptors blood flow 2.1 Biological and endogenous factors mechanosensation RNA Small Interfering Endothelial dysfunction Aetiology vasodilation Mice Knockout Tumor Hydrogen-Ion Concentration Biological Sciences 3. Good health Cell biology Mesenteric Arteries medicine.anatomical_structure lipids (amino acids peptides and proteins) Mechanosensitive channels RNA Interference Shear Strength Endothelium Knockout Biology Nitric Oxide Small Interfering Stress General Biochemistry Genetics and Molecular Biology shear stress Cell Line 03 medical and health sciences G-Protein-Coupled [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system Commentaries Cell Line Tumor Vascular medicine Shear stress Human Umbilical Vein Endothelial Cells Animals Humans Mechanosensation Endothelial Cells vascular biology bacterial infections and mycoses medicine.disease Mechanical Atherosclerosis Mice Inbred C57BL 030104 developmental biology HEK293 Cells Commentary Vascular resistance RNA Calcium Vascular Resistance Endothelium Vascular Stress Mechanical Cellular Developmental Biology |
| Zdroj: | Cell, vol 173, iss 3 Xu, Jie; Mathur, Jayanti; Vessières, Emilie; Hammack, Scott; Nonomura, Keiko; Favre, Julie; et al.(2018). GPR68 Senses Flow and Is Essential for Vascular Physiology.. Cell, 173(3), 762-775.e16. doi: 10.1016/j.cell.2018.03.076. UC San Diego: Retrieved from: http://www.escholarship.org/uc/item/6bx4m237 The Journal of General Physiology Cell Cell, Elsevier, 2018, 173, pp.762-775.e16 |
| ISSN: | 0092-8674 1097-4172 |
| Popis: | International audience; Mechanotransduction plays a crucial role in vascular biology. One example of this is the local regulation ofvascular 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. |
| Databáze: | OpenAIRE |
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