Role of esm-1 in the Development of Sepsis-Induced Acute Kidney Injury

Septic shock corresponds to a life-threatening generalized inflammation observed in the most severe infections. It is a serious and common disease in patients admitted in Intensive Care Units. Acute renal failure is a major complication of septic shock, partly explaining the high mortality rates observed in septic patients. The onset of acute renal failure during septic shock is notably explained by unbalanced kidney inflammation, resulting in the presence of a large number of immune cells in renal compartments. However, the mechanisms involved in the regulation of acute kidney inflammation remain partly unknown. ESM-1 is an anti-inflammatory molecule, preferentially secreted by lungs and kidneys in humans, which could also be involved in the regulation of acute renal inflammation. In this project, we aim to assess if esm-1 plays an anti-inflammatory role in acute renal inflammation in mice. These evaluations will be successively performed in mutant mice that do not express esm-1 and in mice overexpressing esm-1. Using these two models, we propose to determine if esm-1 has a protective effect on kidney when it faces excessive inflammation, as encountered during septic shock. If this hypothesis were confirmed, it could pave the way for novel therapies in the management of septic shock.