Angiotensin-(1-7) and the g protein-coupled receptor MAS are key players in renal inflammation.
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.
Esteban
Vanesa
V
Cellular Biology in Renal Diseases Laboratory, Fundación Jimenez Diaz, Universidad Autónoma Madrid, Madrid, Spain.
Heringer-Walther
Silvia
S
Sterner-Kock
Anja
A
de Bruin
Ron
R
van den Engel
Sandra
S
Wang
Yong
Y
Mezzano
Sergio
S
Egido
Jesus
J
Schultheiss
Heinz-Peter
HP
Ruiz-Ortega
Marta
M
Walther
Thomas
T
D000803:Angiotensin I / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology; D016207:Cytokines; D007249:Inflammation / Q000139:chemically induced / Q000209:etiology*; D007674:Kidney Diseases / Q000209:etiology / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000172:deficiency*; D043562:Receptors, G-Protein-Coupled / Q000172:deficiency*; D015427:Reperfusion Injury / Q000473:pathology
D000959:Antihypertensive Agents; D016207:Cytokines; D016328:NF-kappa B; D010446:Peptide Fragments; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D043562:Receptors, G-Protein-Coupled; D000803:Angiotensin I; C118790:angiotensin I (1-7)