The genetic deletion of the Dual Specificity Phosphatase 3 (DUSP3) attenuates kidney damage and inflammation following ischaemia/reperfusion injury in mouse
| Autor: | Martina Böttner, Géraldine Bolen, Souad Rahmouni, Pascal Rowart, Franziska Theilig, Eileen Dahlke, Matthew P. Stokes, Laurence Poma, François Jouret, Badr Khbouz |
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| Rok vydání: | 2021 |
| Předmět: |
CD31
Male medicine.medical_specialty Physiology Angiogenesis medicine.medical_treatment Ischemia Inflammation Kidney Mice Internal medicine medicine Dual Specificity Phosphatase 3 Animals business.industry Acute kidney injury Endothelial Cells Acute Kidney Injury medicine.disease Nephrectomy Mice Inbred C57BL Endocrinology medicine.anatomical_structure Renal physiology Reperfusion Injury medicine.symptom business |
| Zdroj: | Acta physiologica (Oxford, England)REFERENCES. 234(2) |
| ISSN: | 1748-1716 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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