Adult renal progenitor cells (ARPCs) isolated from human kidney may contribute to repair featuring acute kidney injury (AKI). Bone morphogenetic proteins (BMPs) regulate differentiation, modeling and regeneration processes in several tissues. Aim of the study was to evaluate the biological actions of BMP-2 in ARPCs in vitro and in vivo. BMP-2 was expressed in ARPCs of normal adult human kidney and it was up-regulated in vivo after delayed graft function (DGF) of renal transplant, condition of AKI. ARPCs expressed BMP-Receptors suggesting their potential responsiveness to BMP-2. Incubation of ARPCs with this growth factor enhanced ROS production, NADPH oxidase activity and Nox4 protein expression. In vivo, Nox4 was localized in BMP-2-expressing CD133+ cells at tubular level after DGF. BMP-2 incubation induced α-SMA, collagen-I and fibronectin protein expression in ARPCs. Moreover, α-SMA co-localized with CD133 in vivo after DGF. The oxidative stimulus (H(2)O(2)) induced α-SMA expression in ARPCs, while the anti-oxidant N-acetyl-cysteine inhibited BMP-2-induced α-SMA expression. Nox4 silencing abolished BMP-2-induced NADPH oxidase activation and myofibroblastic induction. We showed that: a) ARPCs express BMP-2; b) this expression is increased in a model of AKI; c) BMP-2 may induce the commitment of ARPCs towards a myofibroblastic phenotype in vitro and in vivo; d) this pro-fibrotic effect is mediated by Nox4 activation. Our findings suggest a novel mechanism linking AKI with progressive renal damage.
BMP-2 INDUCES A PRO-FIBROTIC PHENOTYPE IN ADULT RENAL PROGENITOR CELLS THROUGH Nox4 ACTIVATION
SIMONE, SIMONA;Cariello, M;Sallustio, F;GESUALDO, Loreto;SCHENA, Francesco Paolo;PERTOSA, Giovanni Battista
2012-01-01
Abstract
Adult renal progenitor cells (ARPCs) isolated from human kidney may contribute to repair featuring acute kidney injury (AKI). Bone morphogenetic proteins (BMPs) regulate differentiation, modeling and regeneration processes in several tissues. Aim of the study was to evaluate the biological actions of BMP-2 in ARPCs in vitro and in vivo. BMP-2 was expressed in ARPCs of normal adult human kidney and it was up-regulated in vivo after delayed graft function (DGF) of renal transplant, condition of AKI. ARPCs expressed BMP-Receptors suggesting their potential responsiveness to BMP-2. Incubation of ARPCs with this growth factor enhanced ROS production, NADPH oxidase activity and Nox4 protein expression. In vivo, Nox4 was localized in BMP-2-expressing CD133+ cells at tubular level after DGF. BMP-2 incubation induced α-SMA, collagen-I and fibronectin protein expression in ARPCs. Moreover, α-SMA co-localized with CD133 in vivo after DGF. The oxidative stimulus (H(2)O(2)) induced α-SMA expression in ARPCs, while the anti-oxidant N-acetyl-cysteine inhibited BMP-2-induced α-SMA expression. Nox4 silencing abolished BMP-2-induced NADPH oxidase activation and myofibroblastic induction. We showed that: a) ARPCs express BMP-2; b) this expression is increased in a model of AKI; c) BMP-2 may induce the commitment of ARPCs towards a myofibroblastic phenotype in vitro and in vivo; d) this pro-fibrotic effect is mediated by Nox4 activation. Our findings suggest a novel mechanism linking AKI with progressive renal damage.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
