Altered Expression Profile of Renalα1D-Adrenergic Receptor in Diabetes and Its Modulation by PPAR Agonists

Abstract

Alpha1D-adrenergic receptor (α1D-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 ofα1D-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 ofα1D-AR in rat kidney tissue. Using microarray, we found thatα1D-AR gene was dramatically upregulated in 22-week-old ZD rats compared to ZL controls. Quantitative PCR analysis verified a 16-fold increase inα1D-AR mRNA in renal cortex from ZD animals compared to normal controls. Chronic treatment with fenofibrate or rosiglitazone reduced renal corticalα1D-AR gene. Immunofluorescence staining confirmed thatα1D-AR protein was induced in the glomeruli and tubules of diabetic rats. Moreover, dual immunostaining forα1D-AR and kidney injury molecule-1 indicated thatα1D-AR was expressed in dedifferentiated proximal tubules of diabetic Zucker rats. Taken together, our results show thatα1D-AR expression is upregulated in the diabetic kidneys. PPAR activation suppressed renal expression ofα1D-AR in diabetic nephropathy.