Zhao Xueying, Zhang Yuanyuan, Leander Michelle, Li Lingyun, Wang Guoshen, Emmett Nerimiah
Department of Physiology, Morehouse School of Medicine, Atlanta, GA 30310, USA.
J Diabetes Res. 2014;2014:725634. doi: 10.1155/2014/725634. Epub 2014 Mar 17.
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.
α1D -肾上腺素能受体（α(1D)-AR）在调节由儿茶酚胺介导的生理和病理反应中发挥重要作用，尤其是在心血管和泌尿系统。本研究旨在调查α(1D)-AR在糖尿病肾脏中的表达谱及其受过氧化物酶体增殖物激活受体（PPARs）激活的调节作用。12周龄的Zucker瘦鼠（ZL）和Zucker糖尿病肥胖鼠（ZD）用非诺贝特或罗格列酮治疗8 - 10周。进行基因芯片、实时PCR和共聚焦免疫荧光显微镜检查以评估大鼠肾脏组织中α(1D)-AR的mRNA和蛋白表达。使用基因芯片，我们发现与ZL对照相比，22周龄的ZD大鼠中α(1D)-AR基因显著上调。定量PCR分析证实，与正常对照相比，ZD动物肾皮质中α(1D)-AR mRNA增加了16倍。用非诺贝特或罗格列酮长期治疗可降低肾皮质α(1D)-AR基因。免疫荧光染色证实糖尿病大鼠的肾小球和肾小管中诱导表达α(1D)-AR蛋白。此外，α(1D)-AR和肾损伤分子-1的双重免疫染色表明α(1D)-AR在糖尿病Zucker大鼠去分化的近端小管中表达。综上所述，我们的结果表明糖尿病肾脏中α(1D)-AR表达上调。PPAR激活可抑制糖尿病肾病中α(1D)-AR的肾脏表达。
