Belgique

● Background: DUSP3 is a positive regulator of the innate immune response in case of sepsis, but its role in the ischemic damage is unknown. We study (i) whether and where DUSP3 is expressed in the renal parenchyma, and (ii) whether its genetic deletion in mice (Dusp3-/-) attenuates the ischemic injury. ● Methods: Exp1: Ten C57BL/6 male WT and Dusp3-/- mice underwent right nephrectomy and left renal ischemia(30min)/reperfusion(48h) (I/R). Renal function was assessed upon I/R biomarkers: serum levels of urea (BUN) and creatinine (SCr). The expression of inflammatory markers was quantified at both mRNA and protein levels in ischemic vs. non-ischemic kidneys in WT vs Dusp3-/-. Exp2: Renal resistivity index (RRI) was measured by Doppler ultrasound (n=10 mice). The expression of CD31 and VEGF vascular markers was quantified by qPCR and immuno-staining. ● Results: Exp1: An immuno-reactive signal for DUSP3 was detected in nephrin-positive glomeruli and in Meca-32-positive endothelial cells in both outer and inner medulla, with no immunoreactivity in Dusp3-/- kidneys. Following I/R, the mRNA level of DUSP3 was increased 1.8-fold compared to baseline. Immunoblotting showed a 77-fold increased expression of DUSP3 post I/R. Serum levels of I/R biomarkers were significantly lower in Dusp3-/- compared to WT mice following renal I/R (BUN: 78.4±33.7 vs. 258.9±162.9mg/dL; SCr: 0.1±0.07 vs. 0.8±0.9 mg/dL; p<0.01). At mRNA levels, Dusp3-/- ischemic kidneys showed a significantly decreased expression level of TNF-α, KIM-1, IL-6, IL-1β and caspase-3 compared to WT. PCNA-, F4-80- and CD11b-positive cells were significantly reduced in Dusp3-/- vs WT renal parenchyma post I/R. Exp2: The RRI was lower in Dusp3-/- compared to WT (0.56±0.03 vs. 0.66±0.02; p