Renal epithelial-specific deletion of the Adora2b increases the severity of diabetic nephropathy. Mice with deletion of the Adora2b in vascular endothelia of the kidneys were generated using the Cre-flox system (Adora2bloxP/loxP VE-cadherin-Cre+). Adora2bloxP/loxP VE-cadherin-Cre+ mice and age-, weight-, and sex-matched VE-cadherin-Cre+ mice were subjected to STZ-induced diabetes for 16 weeks before blood, urine, and organs were taken for measurement of (A) albumin excretion, (B) renal nephrin transcript, (C) renal VEGF transcript, and (D) urine MCP-1 (n=6–8 in each group). (E) Extracellular matrix deposition as determined by PAS staining. PAS staining was increased in diabetic PEPCK-Cre+ mice and in Adora2bloxP/loxP VE-cadherin-Cre+ mice (arrows; original magnification, ×400). (F) Histologic score of PAS staining sections. (G) Glomerular size in all groups. (H) Mesangial expansion. G and H show the result of 30 glomeruli in sections of six mice per group. DM, diabetes mellitus. All data are shown as mean±SD.