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.
Department of Physiology, Morehouse School of Medicine, Atlanta, GA 30310, USA.
Xueying
0000-0003-0857-2823
X
Zhao
Department of Physiology, Morehouse School of Medicine, Atlanta, GA 30310, USA.
Yuanyuan
Y
Zhang
Department of Physiology, Morehouse School of Medicine, Atlanta, GA 30310, USA.
Michelle
M
Leander
Department of Physiology, Morehouse School of Medicine, Atlanta, GA 30310, USA.
Lingyun
L
Li
Department of Physiology, Morehouse School of Medicine, Atlanta, GA 30310, USA.
Guoshen
G
Wang
Department of Physiology, Morehouse School of Medicine, Atlanta, GA 30310, USA.
Nerimiah
N
Emmett
D000818:Animals; D054337:Cell Dedifferentiation / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003928:Diabetic Nephropathies / Q000517:prevention & control*; D011345:Fenofibrate / Q000627:therapeutic use; D020869:Gene Expression Profiling; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007684:Kidney Tubules / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D009765:Obesity / Q000150:complications; D047493:PPAR alpha / Q000819:agonists / Q000378:metabolism; D047495:PPAR gamma / Q000819:agonists / Q000378:metabolism; D047492:Peroxisome Proliferator-Activated Receptors / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011924:Rats, Zucker; D018340:Receptors, Adrenergic, alpha-1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000627:therapeutic use; D015854:Up-Regulation / Q000187:drug effects*
C547721:Adra1d protein, rat; D007004:Hypoglycemic Agents; D047493:PPAR alpha; D047495:PPAR gamma; D047492:Peroxisome Proliferator-Activated Receptors; D018340:Receptors, Adrenergic, alpha-1; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D011345:Fenofibrate