Grant: Project Grant

MAP kinases are a family of enzymes that play important roles in the control of cell proliferation, differentiation, migration and adaptation. Accumulating evidence suggests that these enzymes are implicated in the pathogenesis of various human diseases and therefore represent potential therapeutic targets. Our laboratory has identified a novel role of the MAP kinases ERK3 and ERK4 in regulating the inflammatory response and tissue injury. We found that genetic inactivation of ERK3 and ERK4 decreases the production of pro-inflammatory chemokines and ameliorates tissue damage in a mouse model of acute kidney injury. Our results identify ERK3 and ERK4 MAP kinases as novel effectors of the acute kidney injury signaling response. The objective of this project is to characterize the physiopathological roles of ERK3 and ERK4 in acute kidney injury and validate their therapeutic potential. To this end, we have generated genetically-modified mouse models bearing inactivating mutations in the ERK3 and ERK4 genes and developed a small molecule inhibitor of the enzymes. Our proposal has the potential to lead to the validation of novel targets for the treatment of kidney diseases.