Constitutive Atg5 overexpression in mouse bone marrow endothelial progenitor cells improves experimental acute kidney in
- PDF / 2,795,289 Bytes
- 11 Pages / 595.276 x 790.866 pts Page_size
- 78 Downloads / 180 Views
RESEARCH ARTICLE
Open Access
Constitutive Atg5 overexpression in mouse bone marrow endothelial progenitor cells improves experimental acute kidney injury Daniel Patschan1* , Katrin Schwarze2, Björn Tampe2, Jan Ulrich Becker3, Samy Hakroush4, Oliver Ritter1, Susann Patschan1 and Gerhard Anton Müller2
Abstract Background: 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 Atg5 activation in murine EPCs, utilized for AKI therapy. Methods: Ischemic AKI was induced in male C57/Bl6N mice. Cultured murine EPCs were systemically injected postischemia, either natively or after Atg5 transfection (Adenovirus-based approach). Mice were analyzed 48 h and 6 weeks later. Results: Both, 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 postischemic loss of peritubular capillaries. The cells finally augmented the augophagocytic flux in endothelial cells. Conclusions: Constitutive Atg5 activation augments AKI-protective effects of murine EPCs. The exact clinical consequences need to be determined. Keywords: Autophagy, Atg5, EPCs, AKI
Background Syngeneic Proaniogenic Cells (PACs) have been proven as an effective tool in experimental AKI [1–5]. The cells, which in previous years were defined as early Endothelial Progenitor Cells (eEPCs or simply EPCs as oposed to Endothelial Colony Forming Cells – ECFCs; for further references see [6, 7]), have repeatedly been applied in murine AKI, therapeutic effects were robust [1–5]. Own studies performed in the past focused on pharmacological strategies suitable for improving PAC (EPC) * Correspondence: [email protected] 1 Zentrum für Innere Medizin 1 – Kardiologie, Angiologie, Nephrologie, Klinikum Brandenburg, Medizinische Hochschule Brandenburg, Klinikum Brandenburg, Hochstraße 29, 14770 Brandenburg, Germany Full list of author information is available at the end of the article
mediated AKI protection. Numerous substances with agonistic potency were identified [3, 4, 8–10]. Two of our studies addressed the hypothesis that autophagy activation in PACs can increase renoprotective effects of the cells. The term autophagy (AP) describes a process of intracellular protein degradation, it happens under physiological and non-physiological conditions. Certain stimuli, such as substrate deprivation, can augment AP and thus potentially prolong the lifespan of cells [11]. The so-called autophagocytic cascade involves the proteolytic activation of numerous proteins, the Atgs (Autophagy-related proteins) [12]. Meanwhile more than 30 members of the Atg family have been identified. We do not intend to review the hig
Data Loading...
