Project Details
Projekt
Multidimensional profiling of novel mediators and therapeutic targets in AKI during systemic inflammation.
Subject Area
Anaesthesiology
Term
since 2019
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 414847370
Remote ischemic preconditioning (RIPC) has a renoprotective effect and reduces the incidence of acute kidney injury (AKI) in patients undergoing cardiac surgery. The underlying mechanism seems to be based on a transient cell cycle arrest in the renal tubular epithelial cells as self-protective mechanism. Our preliminary data show that damage-associated molecular patterns (DAMPs) as well as other proteins involved in G1 cell cycle arrest are involved in this mechanism, that the renoprotective effects are abolished through the use of propofol and that RIPC may also be effective to prevent AKI caused by systemic inflammation. The overall target is to investigate which molecular mechanisms promote RIPC-induced renal protection to identify novel molecular targets that may be harnessed as new anchor points to develop novel therapeutic approaches for the treatment and/or prevention of AKI, especially in systemic inflammation. In particular, this proposal will address the following specific aims: Aim 1: Validation and mechanistic analysis of novel candidate mediators and therapeutic targets in AKI and RIPC in kidney organoids. Aim 2: Molecular characterization of the role of Bst2 in the pathogenesis of AKI. Aim 3: To investigate whether experimental data can be transferred to the human system and whether RIPC-induced renal protection by DAMPs can be found in sepsis-associated AKI. This research project aims at further unraveling the underlying mechanism of renoprotection in order to find pharmacologic options for the prevention of sepsis-associated AKI. This is urgently needed as mortality in septic patients is very high and is even worse when AKI occurs. By lowering AKI, outcomes of septic patients would improve and expenses of the health-care system could be reduced.
DFG Programme
Clinical Research Units
Subproject of
KFO 342:
Organ Dysfuncion During Systemic Inflammation
