Therapeutic application of activated Protein C epigenetically constrains the redox-enzyme p66shc in diabetic nephropathy

Introduction: Mice with genetically increased levels of activated Protein C (aPC) are protected against diabetic nephropathy and have decreased glomerular expression levels of the mitochondrial-targeted redox enzyme p66shc. In mice therapeutic application of aPC ameliorates indices of diabetic nephropathy and podocyte damage. The therapeutic mechanism and how intermittent application of a plasma protein with a half life of ˜25 min modifies nephropathy remain unknown. Methods: Unilaterally nephrectomized WT mice were STZ-injected. After 4 weeks of diabetes a subgroup was i.p.-injected every other day for 4 weeks…