Inflammation and Immunity Pathways Regulate Genetic Susceptibility to Diabetic Nephropathy

摘要: Diabetic nephropathy (DN) is a leading cause of end-stage renal disease worldwide, but its molecular pathogenesis not well defined, and there are no specific treatments. In humans, strong genetic component determining susceptibility to DN. However, genes controlling DN in humans have been identified. this study, we describe mouse model combining type 1 diabetes with activation the renin-angiotensin system (RAS), which develops robust kidney features resembling human DN: heavy albuminuria, hypertension, glomerulosclerosis. Additionally, powerful effect background regulating nephropathy; 129 strain susceptible disease, whereas C57BL/6 resistant. To examine basis differential susceptibility, analyzed glomerular transcriptome young mice early course their disease. We find dramatic differences regulation immune inflammatory pathways, upregulation proinflammatory pathways (129) coordinate downregulation resistant (C57BL/6) strain. Many these also upregulated rat models Our studies suggest that responses, triggered by hyperglycemia RAS activation, may be critical determinants