Deficiency of hypoxia inducible factor-1α promoted progression of diabetic nephropathy with hypertension.

The present study was designed to investigate the effect of hypoxia inducible factor-1α (HIF-1α) on diabetic nephropathy (DN) with hypertension. HIF-1α deficient mice (Mx/HIF-1α-/- ) were constructed and treated with streptozotocin (STZ) injection for hypertensive DN induction. Normal C57BL/6 mice received STZ or no treatment (normal) were considered as controls. Three days post STZ administration; body weight, fasting blood glucose (FBG), 24 h urinary albumin and systolic blood pressure (SBP) were measured weekly. Periodic acid-Schiff's staining was performed for histologic analysis of glomeruli damage. In comparison with the normal control, significant upregulation and downregulation of HIF-1α was, respectively, detected in diabetic and HIF-1α-/- mice (P<0.01). In comparison with STZ-induced diabetic mice, HIF-1α-/- + STZ mice displayed reduced body weight, and increased FBG, urinary albumin and SBP. PAS showed HIF-1α-/- + STZ mice had damaged kidney tissues, with more renal fibrosis and apparent glomerular hypertrophy. These results demonstrated that HIF-1α deficiency accelerated DN progression with increasing hypertension in mice.