Modulation of gene expression by moxonidine in rats with chronic renal failure.
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 P2Y(2) and P2Y(6), cell cycle regulator p21 and transforming growth factor-beta1 (TGF-beta1), 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 neurotransmitters directly alter expression of these genes in cultured renal cells currently is under investigation.
Vonend
Oliver
O
Marienhospital Herne, Ruhr-Universität Bochum, Hölkeskampring 40, D-44625 Herne, Germany.
Apel
Thomas
T
Amann
Kerstin
K
Sellin
Lorenz
L
Stegbauer
Johannes
J
Ritz
Eberhard
E
Rump
Lars Christian
LC
D000818:Animals; D015306:Biogenic Monoamines / Q000096:biosynthesis; D018450:Disease Progression; D005786:Gene Expression Regulation / Q000187:drug effects*; D007093:Imidazoles / Q000494:pharmacology*; D007676:Kidney Failure, Chronic / Q000503:physiopathology*; D008297:Male; D009392:Nephrectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013564:Sympathetic Nervous System / Q000187:drug effects*; D013565:Sympatholytics / Q000494:pharmacology*
D015306:Biogenic Monoamines; D007093:Imidazoles; D013565:Sympatholytics; C043482:moxonidine