The genetic deletion of the Dual Specificity Phosphatase 3 (DUSP3) attenuates kidney damage and inflammation following ischemia/reperfusion injury in mouse

2021 ◽  
Author(s):  
B. Khbouz ◽  
P. Rowart ◽  
L. Poma ◽  
E. Dahlke ◽  
M. Bottner ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Kidney Damage ◽  
Dual Specificity Phosphatase ◽  
Dual Specificity ◽  
Genetic Deletion

MO329THE GENETIC DELETION OF THE DUAL SPECIFICITY PHOSPHATASE 3 (DUSP3) ATTENUATES KIDNEY DAMAGE FOLLOWING ISCHEMIA/REPERFUSION INJURY IN MOUSE

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Badr Khbouz ◽  
Pascal Rowart ◽  
Laurence Poma ◽  
Martina Bottner ◽  
Géraldine Bolen ◽  
...  
Keyword(s):  
Real Time ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Renal Parenchyma ◽  
Vascular Density ◽  
Mrna Levels ◽  
Dual Specificity Phosphatase ◽  
Dual Specificity ◽  
Genetic Deletion ◽  
Real Time Qpcr

Abstract Background and Aims Dual Specificity Phosphatase 3 (DUSP3) is a positive regulator of the innate immune response in case of sepsis, but its role in the ischemic damage is unknown. Here, we study (i) whether and where DUSP3 is expressed in the renal parenchyma, and (ii) whether its genetic deletion in Dusp3 systemic knock-out (Dusp3-/-) mice attenuates the I/R-associated inflammation and injury. Method Experiment 1: Ten C57BL/6 male WT and Dusp3-/- mice underwent right nephrectomy and left renal ischemia for 30 minutes followed by a reperfusion of 48 hours. Blood and kidneys were collected. Renal function was assessed upon I/R biomarkers, i.e. blood urea nitrogen (BUN) and creatinine (SCr). Expressions of inflammatory and immune markers were comparatively quantified at both mRNA (real-time qPCR) and protein (immuno-blotting and –staining) levels in ischemic vs. non-ischemic kidneys in Dusp3 WT vs. KO mice. Experiment 2: Ten C57BL/6 male WT and Dusp3-/- mice were anesthetized. Renal Doppler ultrasound was performed to assess the renal resistivity index (RRI). The expression of CD31 and VEGF vascular markers was quantified by the means of real-time qPCR and and immuno-staining (FiJi software). Results Experiment 1: An immuno-reactive signal for DUSP3 was detected in the glomeruli (in co-localization with nephrin) and in Meca-32-positive endothelial cells of both outer and inner medulla of mouse non-ischemic WT kidneys. No significant immunoreactivity for DUSP3 was detected in Dusp3-/- kidneys. Following renal I/R, the mRNA level of Dusp3 was increased 1.8-fold compared to baseline (p<0.001). Immunoblot quantifications showed a 77-fold increased expression of DUSP3 post renal 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 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 significantly reduced in Dusp3-/- vs WT renal parenchyma post I/R. Experiment 2: The RRI non-invasively measured by ultrasound was lower in Dusp3-/- group compared to controls (0.56± 0.03 vs. 0.66±0.02; p<0.001). The Dusp3-/- non-ischemic kidneys were characterized by a 1.8-fold increased surface of CD31-positive cells compared to WT kidneys (p<0.001). At mRNA levels, the Dusp3-/- kidneys showed significantly increased basal levels of CD31 and VEGF compared to controls. Conclusion The genetic deletion of DUSP3 is associated with (i) increased renal vascular density, (ii) decreased RRI and (iii) nephroprotection against renal I/R injury.

scholarly journals Endothelial Cell Cystathionine γ‐Lyase Expression Level Modulates Exercise Capacity, Vascular Function, and Myocardial Ischemia Reperfusion Injury

2020 ◽  
Vol 9 (19) ◽  
Author(s):  
Huijing Xia ◽  
Zhen Li ◽  
Thomas E. Sharp ◽  
David J. Polhemus ◽  
Jean Carnal ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Reperfusion Injury ◽  
Exercise Capacity ◽  
Vascular Function ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Genetic Deletion ◽  
Myocardial Ischemia Reperfusion

Background Hydrogen sulfide (H 2 S) is an important endogenous physiological signaling molecule and exerts protective properties in the cardiovascular system. Cystathionine γ‐lyase (CSE), 1 of 3 H 2 S producing enzyme, is predominantly localized in the vascular endothelium. However, the regulation of CSE in vascular endothelium remains incompletely understood. Methods and Results We generated inducible endothelial cell‐specific CSE overexpressed transgenic mice (EC‐CSE Tg) and endothelial cell‐specific CSE knockout mice (EC‐CSE KO), and investigated vascular function in isolated thoracic aorta, treadmill exercise capacity, and myocardial injury following ischemia‐reperfusion in these mice. Overexpression of CSE in endothelial cells resulted in increased circulating and myocardial H 2 S and NO, augmented endothelial‐dependent vasorelaxation response in thoracic aorta, improved exercise capacity, and reduced myocardial‐reperfusion injury. In contrast, genetic deletion of CSE in endothelial cells led to decreased circulating H 2 S and cardiac NO production, impaired endothelial dependent vasorelaxation response and reduced exercise capacity. However, myocardial‐reperfusion injury was not affected by genetic deletion of endothelial cell CSE. Conclusions CSE‐derived H 2 S production in endothelial cells is critical in maintaining endothelial function, exercise capacity, and protecting against myocardial ischemia/reperfusion injury. Our data suggest that the endothelial NO synthase—NO pathway is likely involved in the beneficial effects of overexpression of CSE in the endothelium.

scholarly journals Renal tubular arginase‐2 participates in the formation of the corticomedullary urea gradient and attenuates kidney damage in ischemia‐reperfusion injury in mice

2020 ◽  
Vol 229 (3) ◽  
Author(s):  
Camille Ansermet ◽  
Gabriel Centeno ◽  
Sylviane Lagarrigue ◽  
Svetlana Nikolaeva ◽  
Hikari A. Yoshihara ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Kidney Damage ◽  
Renal Tubular

scholarly journals Ouabain Contributes to Kidney Damage in a Rat Model of Renal Ischemia-Reperfusion Injury

2016 ◽  
Vol 17 (10) ◽  
pp. 1728 ◽  
Author(s):  
Luca Villa ◽  
Roberta Buono ◽  
Mara Ferrandi ◽  
Isabella Molinari ◽  
Fabio Benigni ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Rat Model ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Kidney Damage ◽  
Renal Ischemia ◽  
Renal Ischemia Reperfusion Injury

SP059HEPARANASE A KEY REGULATOR OF THE CHRONIC PROFIBROTIC KIDNEY DAMAGE FOLLOWING ISCHEMIA/REPERFUSION INJURY

2018 ◽  
Vol 33 (suppl_1) ◽  
pp. i365-i365 ◽  
Author(s):  
Valentina Masola ◽  
Simona Granata ◽  
Giovanni Gambrao ◽  
Antonio Lupo ◽  
Gianluigi Zaza
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Kidney Damage

scholarly journals Protective Effect of Ethanol Extract of Celery (Apium graveolens L) on Kidney Damage in Ischemia/ Reperfusion Injury Rats Model

Molekul ◽  
2019 ◽  
Vol 14 (1) ◽  
pp. 11
Author(s):  
Afifah Afifah ◽  
Khusnul Muflikhah ◽  
Viva Ratih Bening Ati ◽  
Rizki Maulana Tsani ◽  
Dairotul Khasanah ◽  
...  
Keyword(s):  
Protective Effect ◽  
Reperfusion Injury ◽  
Rat Model ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Ethanol Extract ◽  
Kidney Damage ◽  
Apium Graveolens ◽  
Tubular Injury ◽  
Injury Score

Ischemia/ reperfusion injury (IRI) is marked by the sudden decrease of blood supply to the kidney followed by restoration of blood flow. Ischemic acute kidney injury (AKI) is the leading cause of morbidity and mortality. Therefore, the prevention strategy for decreasing the damage due to IRI is required. Celery (Apium graveolens L) is often consumed as food. Celery has antioxidant and anti-inflammatory effects. This study aimed to investigate the protective effect of the celery on kidney damage in the kidney ischemia/ reperfusion injury rat model.  Twenty-five rats male, 2-3 months old Sprague Dawley were divided into 5 groups: Group 1  was sham operation, group 2 was ischemia/ reperfusion injury (IRI), group 3, 4, 5 were IRI and 250 mg/kgBW, 500 mg/kgBW, 1000 mg/kgBW of ethanol extract of celery respectively for 14 days before and 3 days after operation. Blood serum sample was taken 3 days after the operation for measuring urea, creatinine, superoxide dismuthase (SOD) and nitrite oxide (NO). Hematoxylin-eosin (HE) staining was utilized to examine kidney tubular injury score. Data were analyzed using One-way ANOVA (p<0,05). The ethanol extract of celery at dose 1000 mg/kgBW prevented the increase of urea, creatinine serum, kidney tubular injury score and prevented the decrease of SOD, NO in the kidney ischemia/ reperfusion injury rat model (p<0,05). In conclusion, the ethanol extract of celery has a protective effect on kidney damage in the ischemia/ reperfusion injury rat model.  

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