[Proteases and antiproteases in the progression of chronic renal insufficiency lesions. The role of the tissue renin-angiotensin system and the renin receptor].
The role of proteases and of antiproteases in the progression of renal disease is well established. Most studies have focused on the serine-proteases of the plasmin/plasminogen activator system and on matrix metalloproteases. Recently, renin, an aspartyl-protease, has attracted much attention because of the role of angiotensin II in the progression of renal lesions and because of the discovery of a functional renin receptor. This receptor is a 45 kDa membrane-protein that binds specifically renin and prorenin. The binding of renin induces an increase of the catalytic efficiency of angiotensinogen conversion into angiotensin I by receptor-bound renin compared to renin in soluble phase, and a rapid phosphorylation of the receptor on serine and tyrosine residues associated with an activation of MAP kinases ERK1/2. Immunofluorescence and confocal analyses on normal human kidney and cardiac biopsies show that the receptor is localized within the mesangial area of glomeruli and in the sub-endothelium of kidney and coronary arteries, associated to smooth-muscle cells. In summary, this receptor exerts dual effects, mediating renin cellular response and increasing the efficiency of angiotensinogen cleavage by membrane-bound renin. These observations emphasizes the importance of angiotensin II generation at the cell surface and the cellular effects of renin add new dimensions (and complexity) to the classical dogma that angiotensin II is the only effector of the RAS.
Nguyen
Geneviève
G
INSERM U489, Hôpital Tenon, 4 rue de la Chine, 75020, Paris.
Burcklé
Céline
C
Sraer
Jean-Daniel
JD
D000804:Angiotensin II / Q000502:physiology; D018450:Disease Progression; D004699:Endocardium / Q000378:metabolism; D010450:Endopeptidases / Q000502:physiology*; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005920:Glomerular Mesangium / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000201:enzymology / Q000473:pathology; D007676:Kidney Failure, Chronic / Q000201:enzymology / Q000473:pathology*; D020935:MAP Kinase Signaling System; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D011480:Protease Inhibitors / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000502:physiology*; D012084:Renin-Angiotensin System / Q000502:physiology*; D012598:Sclerosis; D025262:Vacuolar Proton-Translocating ATPases; D000093342:Prorenin Receptor
D000804:Angiotensin II; D010450:Endopeptidases; D016326:Extracellular Matrix Proteins; D011480:Protease Inhibitors; D011956:Receptors, Cell Surface; D025262:Vacuolar Proton-Translocating ATPases; C458319:ATP6AP2 protein, human; D000093342:Prorenin Receptor