Angiotensin-(1-7) and the g protein-coupled receptor MAS are key players in renal inflammation

• Published in: PloS one Vol. 4; no. 4; p. e5406
• Main Authors: Esteban, Vanesa, Heringer-Walther, Silvia, Sterner-Kock, Anja, de Bruin, Ron, van den Engel, Sandra, Wang, Yong, Mezzano, Sergio, Egido, Jesus, Schultheiss, Heinz-Peter, Ruiz-Ortega, Marta, Walther, Thomas
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 30.04.2009; Public Library of Science (PLoS)
• Subjects: Activation; Adenosine; Analysis; Angiotensin; Angiotensin I - administration & dosage; Angiotensin I - pharmacology; Angiotensin II; Animal models; Animals; Antihypertensive Agents - administration & dosage; Antihypertensive Agents - pharmacology; Apoptosis; Biomedical research; Cancer; Cardiology; Cardiovascular disease; Cellular biology; Chemokines; Chemotherapy; Cytokines; Diabetes; Fibroblasts; Heart; Hypertension; Inflammation; Inflammation - chemically induced; Inflammation - etiology; Inflammatory response; Ischemia; Kidney diseases; Kidney Diseases - etiology; Kidney Diseases - pathology; Kidneys; Laboratories; Localization; Membrane proteins; Mice; Mice, Knockout; Nephrology/Acute Renal Failure; Nephrology/Chronic Kidney Disease; Nephrology/Renal Physiology; NF-kappa B - antagonists & inhibitors; NF-κB protein; Pathology; Peptide Fragments - administration & dosage; Peptide Fragments - pharmacology; Proto-Oncogene Mas; Proto-Oncogene Proteins - deficiency; Receptor mechanisms; Receptors; Receptors, G-Protein-Coupled - deficiency; Renal failure; Renal insufficiency; Reperfusion; Reperfusion Injury - pathology; Rodents; Germany
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0005406

Angiotensin (Ang) II mediates pathophysiologial changes in the kidney. Ang-(1-7) by interacting with the G protein-coupled receptor Mas may also have important biological activities.In this study, renal deficiency for Mas diminished renal damage in models of renal insufficiency as unilateral ureteral obstruction and ischemia/reperfusion injury while the infusion of Ang-(1-7) to wild-type mice pronounced the pathological outcome by aggravating the inflammatory response. Mas deficiency inhibited NF-kappaB activation and thus the elevation of inflammation-stimulating cytokines, while Ang-(1-7) infusion had proinflammatory properties in experimental models of renal failure as well as under basal conditions. The Ang-(1-7)-mediated NF-kappaB activation was Mas dependent but did not involve Ang II receptors. Therefore, the blockade of the NF-kappaB-activating properties of the receptor Mas could be a new strategy in the therapy of failing kidney.