Molecular mechanisms of cell death in renal injury

Chronic kidney disease (CKD) is a cardiovascular risk factor whose progression leads to dialysis/ transplantation. Acute kidney injury (AKI) is a complication of CKD that accelerates progression and mortality is >50%. Therapy of both is unsatisfactory. Understanding the pathogenesis will identify novel therapeutic targets and markers of disease and progression that guide therapy. Cell death plays a key role in renal injury. Regulated necrosis (RN) pathways are raising a key role in renal injury. In this project, we want to study the molecular mechanism of ferroptosis, a subroutine of RN iron dependent. There are evidence that ferroptosis participates in renal injury but the exactly mechanism are unknown. A deeper study of this pathway in renal disease is needed.

General aim: study the regulation of ferroptosis during renal injury and identify new therapeutic targets and new strategies to monitoring the renal disease.

Specific aims: 1) study ferroptosis pathways in kidney, in vivo and in vitro, 2) therapeutic intervention over ferroptosis.

Plan: identify factors promoting ferroptosis in cultured renal cells, in experimental models and in human samples. Confirm the therapeutic relevance of the ferroptosis mediators through functional studies using inhibitors or genetically modified mice.  Our preliminary data suggest that ferroptosis are involved in renal injury and we expect to identify the mechanism of this pathway and find methods for non-invasive monitoring and treatment of renal disease.