Unpublished conference/Abstract (Scientific congresses and symposiums)
Kidney-targeted radiotherapy triggers renal ischaemic preconditioning in mice
Khbouz, Badr; LALLEMAND, François; ROWART, Pascal et al.
2021Autumn Meeting of BELGIAN SOCIETY OF PHYSIOLOGY AND PHARMACOLOGY
 

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Keywords :
renal ischemia; renal physiology; irradiation; preconditionning; angiogenesis; transcriptomics
Abstract :
[en] INTRODUCTION | Renal ischemia/reperfusion (I/R) is the leading cause of acute kidney injury (AKI). Ischemic preconditioning (IPC) may help to attenuate the severity of I/Rassociated AKI. Whole-body irradiation induces renal IPC in mice, although the pathways remain largely unknown. Furthermore, the impact of kidney-centred irradiation on renal resistance against I/R has not been studied. First, we comprehensively investigate the pathways involved in renal irradiation. Next, we assess the functional impact of renal irradiation applied I/R injury. Finally, we test whether Sunitinib-mediated inhibition of the angiogenesis prevents irradiation-associated IPC. METHODS | Exp1: Renal irradiation (8.5Gy) was performed in male C57bl/6 mice(n=10). One month later, total kidney RNA was extracted from irradiated and control (n=5) mice for comparative RNA-Seq. Exp2: After renal irradiation, the right kidneys were removed, and the left kidneys undergo ischemia(30min)/reperfusion(48h) at Days 7-14-28 post irradiation(n=8). Exp3: Following the same protocol of I/R at Day14, 3 groups were compared(n=8): 1/irradiation; 2/irradiation and gavage with Sunitinib from Day2 to 13; 3/control group without irradiation or gavage. RESULTS | Exp1: RNAseq showen up-regulation of angiogenesis signalling pathways. Expressions of angiogenesis markers (CD31, VEGF) showed an increase at both mRNA and protein levels in irradiated kidneys (p<0.01). Exp2: Following I/R, Blood Urea Nitrogen (BUN) and Creatinine (SCr) levels were lower in the irradiated mice compared to controls: (BUN: 86.2±6.8 vs. 454.5±27.2mg/dl; SCr: 0.1±0.01 vs. 1.7±0.2mg/dl, p<0.01). The renal infiltration by CD11b-(187±32 vs 477±20/mm2) and F4-80-positive cells (110±22 vs 212±25/mm2) was reduced in the irradiated group. VEGF and CD31 expression was increased in irradiated kidneys at both mRNA and protein levels(p<0,01). Exp3: One-way analysis of variance followed by Tukey’s test showed that, following I/R, BUN and SCr levels were lower in the irradiated group compared to controls (BUN: 106.1±33.6 vs. 352.2±54.3mg/dl; SCr: 0.3±0.13 vs. 1±0.2mg/dl), and in irradiated group compared to the irradiated-exposed group to Sunitinib (BUN: 106.1±33.6 vs. 408.4±54.9mg/dl; SCr: 0.3±0.12 vs. 1.5±0.3mg/dl; p<0.01). CONCLUSION | Renal irradiation induces the activation of angiogenesis in mice. Renal irradiation leads to IPC, with preserved renal function and attenuated inflammation post I/R. Exposure to the anti-angiogenic drug Sunitinib post-irradiation prevents the irradiation-induced IPC.
Research center :
GIGA‐R - Giga‐Research - ULiège
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 > Département de Physique Médicale > Service médical de radiothérapie
ROWART, Pascal 
POMA, Laurence ;  Centre Hospitalier Universitaire de Liège - CHU > Département de médecine interne > Service de néphrologie
Sounni, Nor Eddine  ;  Université de Liège - ULiège > GIGA Cancer - Tumours and development biology
Noël, Agnes ;  GIGA Cancer > LBTD
JOURET, François  ;  Centre Hospitalier Universitaire de Liège - CHU > Département de médecine interne > Service de néphrologie
Language :
English
Title :
Kidney-targeted radiotherapy triggers renal ischaemic preconditioning in mice
Alternative titles :
[en] Belgique
Publication date :
26 November 2021
Event name :
Autumn Meeting of BELGIAN SOCIETY OF PHYSIOLOGY AND PHARMACOLOGY
Event organizer :
BELGIAN SOCIETY OF PHYSIOLOGY AND PHARMACOLOGY
Event place :
Bruxelles, Belgium
Event date :
26 novembre 2021
Name of the research project :
Impact de l'irradiation dans le préconditionnement ischémique rénal
Funders :
F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE]
Fonds Léon Fredericq [BE]
CHU Liège - Centre Hospitalier Universitaire de Liège [BE]
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since 27 November 2021

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