Abstract
BackgroundEndothelial Progenitor Cells have been shown as effective tool in experimental AKI. Several pharmacological strategies for improving EPC-mediated AKI protection were identified in recent years. Aim of the current study was to analyze consequences of constitutive Atg5 activation in murine EPCs, utilized for AKI therapy.MethodsIschemic AKI was induced in male C57/Bl6N mice. Cultured murine EPCs were systemically injected post-ischemia, either natively or after Atg5 transfection (Adenovirus-based approach). Mice were analyzed 48 h and 6 weeks later.ResultsBoth, native and transfected EPCs (EPCsAtg5) improved persisting kidney dysfunction at week 6, such effects were more pronounced after injecting EPCsAtg5. While matrix deposition and mesenchymal transdifferentiation of endothelial cells remained unaffected by cell therapy, EPCs, particularly EPCsAtg5 completely prevented the post-ischemic loss of peritubular capillaries. The cells finally augmented the augophagocytic flux in endothelial cells.ConclusionsConstitutive Atg5 activation augments AKI-protective effects of murine EPCs. The exact clinical consequences need to be determined.
Highlights
Endothelial Progenitor Cells have been shown as effective tool in experimental Acute Kidney Injury (AKI)
The cells, which in previous years were defined as early Endothelial Progenitor Cells, have repeatedly been applied in murine AKI, therapeutic effects were robust [1,2,3,4,5]
Two of our studies addressed the hypothesis that autophagy activation in Proaniogenic Cells (PACs) can increase renoprotective effects of the cells
Summary
Endothelial Progenitor Cells have been shown as effective tool in experimental AKI. Several pharmacological strategies for improving EPC-mediated AKI protection were identified in recent years. Aim of the current study was to analyze consequences of constitutive Atg activation in murine EPCs, utilized for AKI therapy. The mediators SuberoylAnilide Hydroxamic Acid (SAHA) and Temsirolimus were employed [13], the second study involved the use of MG-132 (proteasome inhibitor) and of zVAD (pan-caspase inhibitor) [14], respectively Both studies, of which the second one was performed in diabetic mice, failed to show sustained beneficial effects of pharmacological preconditioning. A lack of the protein has been documented to aggravate vascular pathology in experimental diabetic nephropathy [17]. Together, these findings clearly suggest a proendothelial role of Atg
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