Article (Scientific journals)
The genetic deletion of the Dual Specificity Phosphatase 3 (DUSP3) attenuates kidney damage following ischemia/reperfusion injury in mouse
Khbouz, Badr; Rowart, Pascal; POMA, Laurence et al.
2021In Acta Physiologica
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Keywords :
ischemia-reperfusion; DUSP3; preconditionning; renal physiology; inflammation; angiogenesis
Abstract :
[en] Aim: Dual Specificity Phosphatase 3 (DUSP3) regulates the innate immune response, with a putative role in angiogenesis. Modulating inflammation and perfusion contributes to renal conditioning against ischemia/reperfusion (I/R). We postulate that the functional loss of DUSP3 is associated with kidney resistance to I/R. Methods: Ten C57BL/6 male WT and Dusp3-/- mice underwent right nephrectomy and left renal I/R (30min/48h). Renal injury was assessed based on serum levels of urea (BUN) and Jablonski score. The expression of CD31 and VEGF vascular markers was quantified by RT-qPCR and immuno-staining. Renal resistivity index (RRI) was measured in vivo by Doppler ultrasound. Comparative phosphoproteomics was conducted using IMAC enrichment of phosphopeptides. Inflammatory markers were quantified at both mRNA and protein levels in ischemic vs. non-ischemic kidneys in WT versus Dusp3-/- . Results: At baseline, we located DUSP3 in renal glomeruli and endothelial cells. CD31-positive vascular network was significantly larger in Dusp3-/- kidneys compared to WT, with a lower RRI in Dusp3-/- mice. Following I/R, BUN and Jablonski score were significantly lower in Dusp3-/- vs. WT mice. Phosphoproteomics highlighted a down-regulation of inflammatory pathways and up-regulation of phospho-sites involved in cell metabolism and VEGF-related angiogenesis in Dusp3-/- vs. WT ischemic kidneys. Dusp3-/- ischemic kidneys showed decreased mRNA levels of CD11b, TNF-α, KIM-1, IL-6, IL-1β and caspase-3 compared to controls. The numbers of PCNA-, F4-80- and CD11b-positive cells were reduced in Dusp3-/- vs. WT kidneys post I/R. Conclusion: Genetic inactivation of Dusp3 is associated with kidney conditioning against I/R, possibly due to attenuated inflammation and improved perfusion.
Research center :
GIGA‐R - Giga‐Research - ULiège
Disciplines :
Urology & nephrology
Author, co-author :
Khbouz, Badr ;  Université de Liège - ULiège > Département des sciences cliniques > Néphrologie
Rowart, Pascal 
POMA, Laurence ;  Centre Hospitalier Universitaire de Liège - CHU > Département de médecine interne > Service de néphrologie
Dahlke, Eileen
Bottner, Martina
Matt, Stokes
Bolen, Geraldine 
Rahmouni, Souad  ;  Université de Liège - ULiège > GIGA Medical Genomics - Unit of Animal Genomics
Theilig, Franziska
JOURET, François  ;  Centre Hospitalier Universitaire de Liège - CHU > Département de médecine interne > Service de néphrologie
Language :
English
Title :
The genetic deletion of the Dual Specificity Phosphatase 3 (DUSP3) attenuates kidney damage following ischemia/reperfusion injury in mouse
Publication date :
27 October 2021
Journal title :
Acta Physiologica
ISSN :
1748-1708
eISSN :
1748-1716
Publisher :
Wiley, Oxford, United Kingdom
Peer reviewed :
Peer Reviewed verified by ORBi
Name of the research project :
Rôle de DUSP3 dans l'ischémie rénale chez la souris
Funders :
F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE]
CHU Liège - Centre Hospitalier Universitaire de Liège [BE]
Fonds Léon Fredericq [BE]
Available on ORBi :
since 29 October 2021

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