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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.

journal of diabetes research

Altered Expression Profile of Renal<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M1"><mml:mrow><mml:msub><mml:mrow><mml:mi mathvariant="bold-italic">α</mml:mi></mml:mrow><mml:mrow><mml:mtext>1</mml:mtext><mml:mtext>D</mml:mtext></mml:mrow></mml:msub></mml:mrow></mml:math>-Adrenergic Receptor in Diabetes and Its Modulation by PPAR Agonists

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