P0535ATG5 OVEREXPRESSION IN PACS SIGNIFICANTLY IMPROVES CELL-MEDIATED AKI PROTECTION

Abstract

Abstract Background and Aims Acute Kidney Injury (AKI) significantly worsens the prognosis of hospitalized patients. Cell-based strategies have been established as reliable option for improving AKI outcomes in experimental AKI. Own studies performed in recent years utilized Pro-angiogenic Cells (PACs). Autophagy (AP) is commonly regarded as process of en-dogenous self-defense. The AP cascade, which may be stimulated by either substrate deprivation or certain exogenous / endogenous stressors, involves the activation of numerous proteins, the so-called Autophagy-related proteins (Atg proteins). Among these, Atg5 has been suggested to play a key role in augmenting AP. The current study evaluated whether selective Atg5 activation in syngeneic murine PACs may result in improved cell-mediated AKI protection. Method Cultured murine PACs were selectively transfected for Atg5. Successful transfection was verified by detecting red fluorescing cells. AKI was induced in male C57/Bl6N mice (8-12 weeks) by bilateral renal ischemia (IRI - 40 minutes). Transfected cells were i.v. injected post-ischemia. Mice were analyzed 48 hours and 6 weeks later. Results IRI induced significant kidney excretory dysfunction as reflected by higher serum cystatin C levels (48 hours and 6 weeks). Cell administration (either native or after transfection) did not improve AKI outcomes at 48 hours. At 6 weeks, injection of native cells resulted in lower serum cystatin C, this effect was even more pronounced if transcfected cells were applied. Conclusion Together, our data show that selective Atg5 overexpression in murine PACs sub-stantially augments cell-mediated AKI protection in the long-term. Thus, a new strategy for improving AKI protective effects of PACs has been identified.