Hyperglycemia enhances kidney cell injury in HIVAN through down-regulation of vitamin D receptors

Abstract In the present study, we evaluated the effect of short term hyperglycemia on renal lesions in a mouse model (Tg26) of HIV-associated nephropathy (HIVAN). Control and Tg26 mice in groups (n = 6) were administered either normal saline (FVBN or Tg) or streptozotocin (FVBN + STZ or Tg26 + STZ). After two weeks, biomarkers were collected and kidneys were harvested. FVBN + STZ and Tg26 + STZ displayed elevated serum glucose levels when compared to FVBN and Tg26 respectively. Tg26 + STZ displayed elevated (P  in vitro studies, HIV down regulated podocyte VDR expression and also enhanced renin angiotensin system activation. In addition, both glucose and HIV stimulated kidney cell ROS generation and DNA damage and compromised DNA repair; however, tempol (superoxide dismutase mimetic), losartan (Ang II blocker) and EB1089 (VDR agonist) provided protection against DNA damaging effects of glucose and HIV. These findings indicated that glucose activated the RAS and inflicted oxidative stress-mediated DNA damage via down regulation of kidney cell VDR expression in HIV milieu both in vivo and in vitro .