Ceramide kinase and its contribution to inflammatory and proliferative kidney diseases

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Ceramide kinase (CerK) is the responsible enzyme for the generation of ceramide-1-phosphate (C1P) which is a still ill defined second messenger that has been attributed certain cellular functions such as feeding into the prostaglandin cascade and participating in cell proliferation. In this project we plan to investigate the signalling capacity of this sphingolipid-derived mediator in the setting of inflammatory and proliferative kidney diseases. Especially, we will address (1) the impact of phosphorylation reactions on CerK activity in vitro and in intact renal cells and identify the relevant protein kinases. Furthermore, we will study (2) the regulation of CerK expression in renal cells including glomerular mesangial cells, podocytes and Wilms tumor cells, and unravel its contribution to proinflammatory and proliferative cell responses by using a pharmacological inhibitor of the enzyme, by depletion studies, and by investigating CerK deficient mice. Finally, these cell culture experiments will be complemented (3) by in vivo studies on animal models of chronic inflammatory kidney diseases. In summary, these studies will clarify whether the CerK could serve as a new therapeutic target in the treatment of inflammatory and proliferative kidney diseases.