New molecular mechanisms of inflammation in renal diseases
Pathophysiology and Therapy of Immune and Inflammatory Diseases
Hospital Universitario Fundación Jiménez Díaz
DESCRIPTION OF THE OFFER
PI: Alberto Ortiz (https://scholar.google.com/citations?user=1IKOVx0AAAAJ). 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. Inflammation and cell death play a key role in renal injury, and both mechanisms are tightly related. In this project, we will characterize molecular mechanisms of inflammation activated as result of cell death during AKI. There is evidence that regulated necrosis can promote an inflammatory response during AKI. A deeper study of this mechanism in renal disease is needed to design novel therapeutics strategies, which may also apply to other forms of tissue injury.
General aim: to characterize the role of regulated necrosis on the generation of the inflammation loop of tissue injury amplification during renal injury and to identify new therapeutic targets and new strategies to monitoring the response to therapy of renal disease.
Specific aims: 1) characterize the effect of ferroptosis and necroptosis on renal inflammation in vivo and in vitro, 2) develop novel forms of therapeutic intervention.
Plan: to study the effect of inhibitors of cell death over inflammation in cultured renal cells and in experimental models of AKI. Identify the keys proteins and mechanisms associated to regulated necrosis that trigger the inflammatory response in experimental AKI. Our preliminary data suggest that ferroptosis is involved in triggering renal inflammation and we expect to find methods for non-invasive monitoring and treatment of renal disease. These methods may also apply to other forms of kidney injury
Ana Belen Sanz Bartolome