[en] Renal ischemia/reperfusion (I/R) causes acute kidney injury (AKI). Ischemic preconditioning (IPC) attenuates I/R-associated AKI. Whole-body irradiation induces renal IPC in mice. Still, the mechanisms remain largely unknown. Furthermore, the impact of kidney-centered irradiation on renal resistance against I/R has not been studied. Renal irradiation (8.5Gy) was done in male 8-12-week-old C57bl/6 mice using Small Animal Radiation Therapy (SmART) device. Left renal I/R was performed by clamping the renal pedicles for 30 minutes, with simultaneous right nephrectomy, at 7, 14, and 28 days post-irradiation. The renal reperfusion lasted 48 hours. Following I/R, blood urea nitrogen (BUN) and creatinine (SCr) levels were lower in pre-irradiated mice compared to controls, so was the histological Jablonski score of AKI. The metabolomics signature of renal I/R was attenuated in pre-irradiated mice. The numbers of PCNA-, CD11b-, and F4-80-positive cells in the renal parenchyma post-I/R were reduced in pre-irradiated versus control groups. Such an IPC was significantly observed as early as D14 post-irradiation. RNA-Seq showed an up-regulation of angiogenesis- and stress response-related signaling pathways in irradiated non-ischemic kidneys at D28. RT-qPCR confirmed the increased expression of VEGF, ALK5, HO1, PECAM1, NOX2, HSP70, and HSP27 in irradiated kidneys compared to controls. In addition, irradiated kidneys showed an increased CD31-positive vascular area compared to controls. A 14-day gavage of irradiated mice with the anti-angiogenic drug Sunitinib before I/R abrogated the irradiation-induced IPC at both functional and structural levels. Our observations suggest that kidney-centered irradiation activates pro-angiogenic pathways and induces IPC, with preserved renal function and attenuated inflammation post-I/R.
Disciplines :
Urology & nephrology
Author, co-author :
Khbouz, Badr ; Université de Liège - ULiège > Département des sciences cliniques > Néphrologie
LALLEMAND, François ; Centre Hospitalier Universitaire de Liège - CHU > > Service médical de radiothérapie
Cirillo, Arianna ; Université de Liège - ULiège > Unités de recherche interfacultaires > Centre Interdisciplinaire de Recherche sur le Médicament (CIRM)
Rowart, Pascal ; Université de Liège - ULiège > Département des sciences cliniques > Néphrologie ; Department of Pharmacology and Chemical Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, United States
Legouis, David; Division of Intensive Care, Department of Acute Medicine, Geneva University Hospitals, Geneva, Switzerland ; Laboratory of Nephrology, Department of Medicine and Cell Physiology, University Hospital and University of Geneva, Geneva, Switzerland
Noël, Agnès ; Université de Liège - ULiège > GIGA > GIGA Cancer
De Tullio, Pascal ; Université de Liège - ULiège > Unités de recherche interfacultaires > Centre Interdisciplinaire de Recherche sur le Médicament (CIRM)
de Seigneux, Sophie; Laboratory of Nephrology, Department of Medicine and Cell Physiology, University Hospital and University of Geneva, Geneva, Switzerland
JOURET, François ; Centre Hospitalier Universitaire de Liège - CHU > > Service de néphrologie
Language :
English
Title :
Kidney-targeted irradiation triggers renal ischaemic preconditioning in mice.
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