NDT Advance Access originally published online on July 20, 2004
Nephrology Dialysis Transplantation 2004 19(9):2217-2222; doi:10.1093/ndt/gfh374
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Nephrol Dial Transplant Vol. 19 No. 9 © ERA-EDTA 2004; all rights reserved
Original Article
Modulation of gene expression by moxonidine in rats with chronic renal failure
1 Department of Internal Medicine, Marienhospital Herne, University of Bochum, 2 Department of Pathology,University of Erlangen and 3 Department of Nephrology, University of Heidelberg, Germany
Correspondence and offprint requests to: Professor Dr L. C. Rump, Marienhospital Herne, Ruhr-Universität Bochum, Hölkeskampring 40, D-44625 Herne, Germany. Email: christian.rump{at}ruhr-uni-bochum.de
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 real-time 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 P2Y2 and P2Y6, cell cycle regulator p21 and transforming growth factor-ß1 (TGF-ß1), and a decrease of the metalloprotease aminopeptidase-M (APM), membrane transporter megalin, ageing-related klotho, type I TGF-ß receptor, mitochondrial cytochrome oxidase-1, kallikrein, leucine zipper-1, matrix-degrading metalloprotease meprin, the organic anion transporter and the P2 receptor subtypes P2Y1 and P2Y4. In SNX-M rats, mRNA levels of APM, megalin, klotho, TGF-ß1, type I TGF-ß receptor, p21, P2Y1 and P2Y2 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 neurotransmitters directly alter expression of these genes in cultured renal cells currently is under investigation.
Keywords: 5/6 nephrectomy; chronic renal failure; gene expression; moxonidine; P2 receptors; sympathetic activity
*These authors contributed equally to this work.
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