Background: In the present study, we investigated the potential effect of aliskiren on smooth muscle cell (SMC) migration in response to prorenin. Methods: Cultured human SMCs were incubated with angiotensinogen (ANG) (1.5 10<sup>-7</sup>M) and increasing concentrations of aliskiren (10<sup>-6</sup>10<sup>-5</sup>M). After 24 h, SMC migration was assessed by Boydens chamber chemotactic assay using prorenin as chemotactic factor (10<sup>-8</sup>M). The effect of aliskiren on RhoA and Rac activity was also determined by G-LISA assay and the lamellipodia formation by rhodaminephalloidin staining. Changes in cell morphology were recorded in real-time using the iCelligence system. Results: Aliskiren determined, at 10<sup>-5</sup>M, a significant inhibition of SMC migration induced by prorenin (-66.418.1%; p > 0.05), while no significant effect was observed when PDGF-BB was utilized as chemotactic agent. Aliskiren also reduced Rac-GTP levels in response to prorenin (-54.2±5.4%) without affecting the RhoA-GTP levels. Finally, aliskiren inhibited both the lamellipodia formation and morphological changes induced by prorenin with no significant effect on PDGF-BB activity. Conclusions: Taken together, we provide the first evidence of the inhibitory action of aliskiren on SMC migration induced by prorenin.

Aliskiren inhibits prorenin-induced human aortic smooth muscle cell migration / N. Ferri, F. Panariti, C. Ricci, G. Maiocchi, A. Corsini. - In: JRAAS. - ISSN 1470-3203. - 16:2(2015), pp. 284-291. [10.1177/1470320314528364]

Aliskiren inhibits prorenin-induced human aortic smooth muscle cell migration

N. Ferri;C. Ricci;A. Corsini
2015

Abstract

Background: In the present study, we investigated the potential effect of aliskiren on smooth muscle cell (SMC) migration in response to prorenin. Methods: Cultured human SMCs were incubated with angiotensinogen (ANG) (1.5 10-7M) and increasing concentrations of aliskiren (10-610-5M). After 24 h, SMC migration was assessed by Boydens chamber chemotactic assay using prorenin as chemotactic factor (10-8M). The effect of aliskiren on RhoA and Rac activity was also determined by G-LISA assay and the lamellipodia formation by rhodaminephalloidin staining. Changes in cell morphology were recorded in real-time using the iCelligence system. Results: Aliskiren determined, at 10-5M, a significant inhibition of SMC migration induced by prorenin (-66.418.1%; p > 0.05), while no significant effect was observed when PDGF-BB was utilized as chemotactic agent. Aliskiren also reduced Rac-GTP levels in response to prorenin (-54.2±5.4%) without affecting the RhoA-GTP levels. Finally, aliskiren inhibited both the lamellipodia formation and morphological changes induced by prorenin with no significant effect on PDGF-BB activity. Conclusions: Taken together, we provide the first evidence of the inhibitory action of aliskiren on SMC migration induced by prorenin.
Migration; small GTPases; smooth muscle cells; prorenin; Rac
Settore BIO/14 - Farmacologia
2015
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/588886
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