Ischemia-reperfusion (I/R) injury of the kidney is one of the primary causes of acute kidney injury. It is associated with severe morbidity and mortality and thus represents a major socioeconomic health problem. It is a consequence of a variety of different injurious insults in native kidneys (e.g. during cardiac surgery). Moreover, it is commonly associated with the transplantation procedure and thus an unavoidable phenomenon in transplanted kidneys 1. During ischemic acute kidney injury a transient drop in blood flow to the kidney is followed by a reperfusion period. Reperfusion itself, though vital to a restoration of kidney function, is associated with significant additional cellular injury 2. We have recently summarized the deleterious events resulting from I/R-injury 3. The damage inflicted by tissue ischemia is subsequently aggravated by a dramatic surge in reactive oxygen and nitrogen species during reperfusion. These induce protein modifications, lipid oxidations, and DNA double strand breaks finally culminating in endothelial dysfunction, neutrophil adherence to endothelium and trans-endothelial migration, the release of inflammatory mediators, cellular calcium overload and eventually cell death 3. In the kidney blood flow to the outer medulla is disproportionately reduced with respect to the reduction in total blood flow. Thus, epithelial cell injury is mainly detected in the S3 segment of the proximal tubule, located in the outer medulla. Interplay of several events contributes to the cellular injury observed in the kidney. The damaged endothelium interacts with and activates inflammatory cells through enhanced expression of adhesion molecules (e.g. ICAM-1, selectins) 4. This interaction in turn contributes to obstruction of capillaries and postcapillary venules, further activation and transmigration of leukocytes, production of cytokines and inflammation in tubular epithelial cells 5. Capillary rarefaction in the inner stripe of the outer medulla ensues, which due to the development of chronic hypoxia is an important contributor to post-AKI tubule-interstitial fibrosis and progression to chronic kidney disease 4. Cell polarity and cytoskeletal arrangement is severely impaired in proximal tubular epithelial cells during ischemia 4. Important phenotypical changes are loss of the proximal tubule brush border as well as loss of polarity and derangement of adhesion molecules and other membrane proteins and disruption of cell-cell interactions at adherent and tight junctions 4. MicroRNAs (miRNAs) are currently under intense investigation as powerful regulators of various diseases with potential critical impact on disease initiation and/or progression, including kidney disease 5. MiRNAs represent small non-coding RNA transcripts with a length of ~22 nucleotides, which through post-transcriptional binding of the 3′-untranslated region (UTR) of mRNA targets lead to the repression of gene/protein expression and/or translational inhibition of protein synthesis 5. The first miRNA, lin-4, was discovered while investigating genetic loci responsible for temporal patterning in Caenorrhabdidits elegans 5. Intriguingly, a single microRNA may alter the expression of a large number of target genes, thus influencing a specific pathology by regulating whole disease-specific pathways and signalling cascades rather than a single gene. This unique function underlines the immense importance of these small molecules. The biogenesis of microRNAs follows a tightly regulated pattern 5. Following transcription in the nucleus miRNA precursors are transported into the cytosol, where they are further processed by a ribonuclease, named DICER 5. Mature miRNAs finally interact in the so called RNA-induced silencing complex (RISC) with cognate sequences in the 3′-untranslated region (3′-UTR) of their target mRNAs 8. MiRNA antagonists (antimiRs) are available to specifically cleave mature miRNAs, thereby silencing their cellular effects and thus serve as powerful novel therapeutics of many diseases 5. Our group is interested in the mechanisms of microRNA mediated kidney injury. These short, noncoding RNA molecules are involved in a variety of different biological processes such as proliferation, apoptosis and differentiation. We aim to identify novel microRNAs in different mouse models of kidney injury and elucidate involved signaling pathways. We are interested in modulating pathological microRNA expression by RNA therapeutics, termed antagomirs, which enable specific targeting and cleavage of miRNAs and thus modulation of pathological signaling pathways in vivo. In addition, microRNAs are released into the extracellular compartment (blood and urine) in patients. Thus, circulating microRNAs may serve as a non-invasive tool to detect and monitor disease activity 6. We also aim to investigate the release pattern of circulating microRNAs.