Chemotactic effect of prorenin on human aortic smooth muscle cells: a novel function of the prorenin receptor
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Data di Pubblicazione:
2011
Citazione:
Chemotactic effect of prorenin on human aortic smooth muscle cells: a novel function of the prorenin receptor / N. Ferri, C.M. Greco, M. Camera, L. Facchinetti, M. Brambilla, S. Pellegrino, M.L. Gelmi, E. Tremoli, A. Corsini. ((Intervento presentato al 25. convegno Congresso Nazionale della Società Italiana per lo Studio dell’Aterosclerosi (SISA) tenutosi a Roma nel 2011.
Abstract:
The discovery of a specific prorenin receptor has opened to a possible biological function of prorenin independently from angiotensin I production. In the present study we show that prorenin receptor is expressed in normal human vessels (mammary arteries and saphenous veins) and in cultured human aortic smooth muscle cells, by western blotting, quantitative real time PCR and immunocytochemistry analysis. Prorenin (10 nmol/L) exerted a 3 fold induction of smooth muscle cell migration assessed by Boyden chamber chemotaxis assay after 6h stimulation and a 30% increase of smooth muscle cell random motility determined by video microscopy. The prorenin decoy peptide (10 mol/L) almost completely inhibited smooth muscle cell migration in response to prorenin, while no effect was observed with a scrambled peptide. Knock down of prorenin receptor by small interfering RNA completely affected the migratory response of smooth muscle cells to prorenin. Prorenin increased focal adhesion size (+42.8±23.0%) and RhoA activation (+15.0±5.0%) after 10 minutes stimulation associated with cleavage of the focal adhesion kinase (pp125FAK) at 60 minutes. The generation of a 50kDa fragment of pp125FAK was suppressed by the calpain inhibitor ALLN (100 mol/L), which also inhibited smooth muscle cell migration in response to prorenin. Thus, in the present report we show that prorenin is expressed in human vessels and in cultured smooth muscle cells where it exerts a chemotactic action. This effect is associated with a profound cytoskeleton and focal adhesion re-organization, RhoA activation and calpain-mediated pp125FAK cleavage.
Tipologia IRIS:
14 - Intervento a convegno non pubblicato
Elenco autori:
N. Ferri, C.M. Greco, M. Camera, L. Facchinetti, M. Brambilla, S. Pellegrino, M.L. Gelmi, E. Tremoli, A. Corsini
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