Altered Expression Profile of Renal α (1D)-Adrenergic Receptor in Diabetes and Its Modulation by PPAR Agonists

Alpha(1D)-adrenergic receptor (α (1D)-AR) plays important roles in regulating physiological and pathological responses mediated by catecholamines, particularly in the cardiovascular and urinary systems. The present study was designed to investigate the expression profile of α (1D)-AR in the diabetic kidneys and its modulation by activation of peroxisome proliferator-activated receptors (PPARs). 12-week-old Zucker lean (ZL) and Zucker diabetic fatty (ZD) rats were treated with fenofibrate or rosiglitazone for 8–10 weeks. Gene microarray, real-time PCR, and confocal immunofluorescence microscopy were performed to assess mRNA and protein expression of α (1D)-AR in rat kidney tissue. Using microarray, we found that α (1D)-AR gene was dramatically upregulated in 22-week-old ZD rats compared to ZL controls. Quantitative PCR analysis verified a 16-fold increase in α (1D)-AR mRNA in renal cortex from ZD animals compared to normal controls. Chronic treatment with fenofibrate or rosiglitazone reduced renal cortical α (1D)-AR gene. Immunofluorescence staining confirmed that α (1D)-AR protein was induced in the glomeruli and tubules of diabetic rats. Moreover, dual immunostaining for α (1D)-AR and kidney injury molecule-1 indicated that α (1D)-AR was expressed in dedifferentiated proximal tubules of diabetic Zucker rats. Taken together, our results show that α (1D)-AR expression is upregulated in the diabetic kidneys. PPAR activation suppressed renal expression of α (1D)-AR in diabetic nephropathy.