Final Report Summary - DNCURE (Dynamic signalling networks in Diabetic Nephropathy (DN)– New avenues to a personalized therapy.-)
Diabetes is an escalating problem worldwide and a major cause of vascular disease and renal failure. Diabetic nephropathy (DN) accounts for about 30-50% of new patients requiring renal replacement therapy and there is an urgent need to develop new therapeutic strategies. Current therapeutical interventions including glycemic and blood pressure control cannot stop or reverse the progression of DN. To this end, we developed novel techniques such as a Drosophila diabetes models and high efficiency purification protocols of native kidney cells to systematically unravel DN related glomerular signaling networks aiming to reveal new therapeutic, preventive and regenerative strategies for the cure of DN.
Deep RNA and proteomic profiling established a podocyte atlas and a basis for targeted screening in Drosophila nephrocytes in a diabetic milieu. While we found that the regeneration capacity of podocytes is very limited, we identified specific metabolic alterations of these specialized renal epithelial cells that control cell fate and maintenance in response to a diabetic environment. Targeted interference of these aberrant metabolic pathways allowed to halt the cellular hypertrophy and de-differentiation which ultimately lead to progressive functional renal decline. Thus, our data suggested a novel treatment strategy aiming to correct intracellular metabolic dysfunctions.
Deep RNA and proteomic profiling established a podocyte atlas and a basis for targeted screening in Drosophila nephrocytes in a diabetic milieu. While we found that the regeneration capacity of podocytes is very limited, we identified specific metabolic alterations of these specialized renal epithelial cells that control cell fate and maintenance in response to a diabetic environment. Targeted interference of these aberrant metabolic pathways allowed to halt the cellular hypertrophy and de-differentiation which ultimately lead to progressive functional renal decline. Thus, our data suggested a novel treatment strategy aiming to correct intracellular metabolic dysfunctions.