Modulation of gene expression by moxonidine in rats with chronic renal failure
Modulation of gene expression by moxonidine in rats with chronic renal failure
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DOI：
10.1093/ndt/gfh374
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发表时间：
2004-09-01
影响因子：
6.1
通讯作者：
Rump, LC
中科院分区：
文献类型：
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作者：
Vonend, O;Apel, T;Rump, LC
背景。交感神经过度活跃是慢性肾衰竭的标志。在先前的实验研究中，交感神经溶解药物莫索尼定（MOX）对慢性肾功能衰竭的进展有有益的影响。本研究探讨莫昔定是否会影响亚全肾切除大鼠肾脏适应性变化相关基因的表达。从假手术、半全肾切除（SNX）和莫索尼定治疗的SNX （SNX- m）大鼠术后12周的残肾中分离RNA。选择可能在肾大部切除术后肾脏适应过程中起作用的基因，并采用实时逆转录聚合酶链反应（RT-PCR）分析其表达。肾次全切除术后，半胱氨酸蛋白酶组织蛋白酶（H+L）、ATP受体亚型P2Y(2)和P2Y(6)、细胞周期调节因子p21和转化生长因子- β 1 （tgf - β）的基因表达增加，金属蛋白酶氨基肽酶- m （APM）、膜转运蛋白meggalin、衰老相关klotho、I型tgf - β受体、线粒体细胞色素氧化酶-1、小肽素、亮氨酸zipper-1、基质降解金属蛋白酶meprin、有机阴离子转运体和P2受体亚型P2Y(1)和P2Y(4)。SNX-M大鼠的APM、meggalin、klotho、tgf - β 1、I型tgf - β受体、p21、P2Y(1)和P2Y(2) mRNA水平向对照水平回落。在残肾中发现了几个在次全肾切除术后表达水平改变的基因。这些基因可能是促进疾病进展的候选基因。在不影响血压的浓度下，交感神经解药莫onidine可调节其中一些基因的肾脏表达回到控制水平。在培养的肾细胞中，交感神经递质直接改变这些基因表达的程度目前还在研究中。
Background. Sympathetic overactivity is a hallmark of chronic renal failure. In a previous experimental study, the sympatholytic drug moxonidine (MOX) had beneficial effects on progression of chronic renal failure. The present study investigates whether moxonidine influences the expression of genes associated with adaptive changes in kidneys of subtotally nephrectomized rats.Methods. RNA was isolated from remnant kidneys of sham-operated, subtotally nephrectomized (SNX) and moxonidine-treated SNX (SNX-M) rats 12 weeks after operation. Genes that might play a role in renal adaptation processes after subtotal nephrectomy were selected and their expression was analysed by realtime reverse transcription-polymerase chain reaction (RT-PCR).Results. After subtotal nephrectomy, there was an increase in gene expression of cysteine protease cathepsin (H+L), ATP receptor subtypes P2Y(2) and P2Y(6), cell cycle regulator p21 and transforming growth factor-beta1 (TGF-betaI), and a decrease of the metalloprotease aminopeptidase-M (APM), membrane transporter megalin, ageing-related klotho, type I TGF-beta receptor, mitochondrial cytochrome oxidase-1, kallikrein, leucine zipper-1, matrix-degrading metalloprotease meprin, the organic anion transporter and the P2 receptor subtypes P2Y(1) and P2Y(4). In SNX-M rats, mRNA levels of APM, megalin, klotho, TGF-beta1, type I TGF-beta receptor, p21, P2Y(1) and P2Y(2) were shifted back towards control levels.Conclusions. Several genes showing altered expression levels after subtotal nephrectomy were identified in remnant kidneys. These genes might act as candidates to promote disease progression. The sympatholytic drug moxonidine, at a concentration devoid of blood pressure effects, regulates the renal expression of some of these genes back towards control levels. To what extent sympathetic neuro transmitters directly alter expression of these genes in cultured renal cells currently is under investigation.