Sirt6 deficiency aggravates angiotensin II-induced cholesterol accumulation and injury in podocytes.

摘要: Disturbed renal lipid metabolism, especially cholesterol dysregulation plays a crucial role in the pathogenesis of chronic kidney disease (CKD). We recently reported that angiotensin (Ang) II could induce accumulation and injury podocytes. However, underlying mechanisms for these alterations remain unknown. Methods: Bioinformatics analysis biopsy specimens from patients with hypertensive nephropathy (HN) suggests involvement Sirtuin 6 (Sirt6) Ang II-induced glomerular cholesterol. Using podocyte-specific Sirt6 knockout mouse model, effects on podocytes therapeutic efficacies cholesterol-lowering agents were evaluated. Results: Cholesterol was detected II-infused mice, whereas selective deletion not only increased cells but also exacerbated injury. Deletion attenuated protective effect cyclodextrin (CD) urinary albumin excretion, glomerulosclerosis podocyte In addition, we demonstrated affected efflux by regulating expression ATP-binding cassette transporter G1 (ABCG1). Conclusions: These findings provide evidence is potential target renin-angiotensin system (RAS)-associated rationale application CKD.