|
Sign In to gain access to subscriptions and/or personal tools.
|
Role of proteinuria in the regulation of renal renin-angiotensin system components in unilateral proteinuric rats
Leo E Deelman
Department of Clinical Pharmacology, Groningen University Institute for Drug Exploration, University of Groningen, Groningen, The Netherlands, l.e.deelman{at}med.rug.nl
Gerjan Navis
Department of Nephrology, University Hospital, Groningen, The Netherlands
Erik de Boer
Department of Nephrology, University Hospital, Groningen, The Netherlands
Mirian Wietses
Department of Clinical Pharmacology, Groningen University Institute for Drug Exploration, University of Groningen, Groningen, The Netherlands
Dick de Zeeuw
Department of Clinical Pharmacology, Groningen University Institute for Drug Exploration, University of Groningen, Groningen, The Netherlands
Robert H Henning
Department of Clinical Pharmacology, Groningen University Institute for Drug Exploration, University of Groningen, Groningen, The Netherlands
Renin-angiotensin system (RAS) overactivity has been implied in progressive renal function loss. We investigated whether changes in the renal expression of RAS components are specifically associated with the proteinuric kidney.
Unilateral adriamycin-induced proteinuria was obtained by clamping the left renal artery before injection of adriamycin. In control animals, both left and right renal arteries were clamped. Twelve weeks later, mRNA expression of RAS components was determined in both kidneys. In the affected and non-affected kidney of the unilateral proteinuric rat, we demonstrate up-regulation of angiotensin-converting enzyme (ACE) mRNA (213%±22 and 188%±24 of controls, respectively), up-regulation of transforming growth factor (TGF- ) mRNA (956%±229 and 418%±56) and down-regulation of angiotensin type 2 receptor (AT2-R) mRNA (24%±5 and 20%±5). The expression of angiotensin type 1 receptor (AT1-R) mRNA and inositol 1,4,5-trisphosphate receptor type I (IP3R-I) mRNA were unchanged.
In conclusion, renal expression of ACE, AT2-R, and AT1-R mRNA is not mediated by protein leakage. Local intrarenal protein leakage did influence renal TGF- mRNA expression.
Key Words: adriamycin • rats • angiotensin • ACE • transforming growth factor ß
References
- Remuzzi G., BertaniT. Is glomerulosclerosis a consequence of altered glomerular permeability to macromolecules? Kidney Int 1990;38:384-94.[Web of Science][Medline]
[Order article via Infotrieve]
- de-Keijzer MH, Provoost AP, Molenaar JC Proteinuria is an early marker in the development of progressive renal failure in hypertensive fawn-hooded rats. J Hypertens 1989;7:525-8.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- De Boer E., Navis G.,Tiebosch AT, De Jong PE, de Zeeuw D. Systemic factors are involved in the pathogenesis of proteinuria-induced glomerulosclerosis in adriamycin nephrotic rats. J Am Soc Nephrol 1999;10:2359-66.[Abstract/Free Full Text]
- The GISEN Group (Gruppo Italiano di Studi Epidemiologici in Nefrologia). Randomised placebo-controlled trial of effect of ramipril on decline in glomerular filtration rate and risk of terminal renal failure in proteinuric, non-diabetic nephropathy. Lancet 1997;349:1857-63.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Wapstra FH, Navis G., De Jong PE, de Zeeuw D. Chronic angiotensin II infusion but not bradykinin blockade abolishes the antiproteinuric response to angiotensin-converting enzyme inhibition in established adriamycin nephrosis. J Am Soc Nephrol 2000;11:490-6.[Abstract/Free Full Text]
- Wapstra FH, Van Goor H., Navis GJ, De Jong PE, de Zeeuw D. Antiproteinuric effect predicts renal protection by angiotensin-converting enzyme inhibition in rats with established adriamycin nephrosis. Clin Sci (Colch) 1996;90:393-401.[Medline]
[Order article via Infotrieve]
- Maschio G., Alberti D., Janin G. et al. Effect of the angiotensin-converting-enzyme inhibitor benazepril on the progression of chronic renal insufficiency. The AngiotensinConverting-Enzyme Inhibition in Progressive Renal Insufficiency Study Group. N Engl J Med 1996;334:939-45.[Abstract/Free Full Text]
- Gray MO, Long CS, Kalinyak JE, Li HT, Karliner JS Angiotensin II stimulates cardiac myocyte hypertrophy via paracrine release of TGF-beta 1 and endothelin-1 from fibroblasts. Cardiovasc Res 1998;40:352-63.[Abstract/Free Full Text]
- Gibbons GH, Pratt RE, Dzau VJ Vascular smooth muscle cell hypertrophy vs. hyperplasia. Autocrine transforming growth factor-beta 1 expression determines growth response to angiotensin II. J Clin Invest 1992;90:456-61.response[Web of Science][Medline]
[Order article via Infotrieve]
- Griendling KK, Berk BC, Socorro L., Tsuda T., Delafontaine P., Alexander RW Secondary signalling mechanisms in angiotensin II-stimulated vascular smooth muscle cells. Clin Exp Pharmacol Physiol 1988;15:105-12.[Web of Science][Medline]
[Order article via Infotrieve]
- Baroni EA, Costa RS, Volpini R., Coimbra TM Sodium bicarbonate treatment reduces renal injury, renal production of transforming growth factor-beta, and urinary transforming transforming growth factor-beta, and urinary transforming growth factor-beta excretion in rats with doxorubicin-induced nephropathy. Am J Kidney Dis 1999;34:328-37.[Web of Science][Medline]
[Order article via Infotrieve]
- Sharma K., Wang L., Zhu Y., Bokkala S., Joseph SK Transforming growth factor-beta1 inhibits type I inositol 1,4,5-trisphosphate receptor expression and enhances its phosphorylation in mesangial cells. J Biol Chem 1997;272:14617-23.[Abstract/Free Full Text]
- Sharma K., Jin Y., Guo J., Ziyadeh FN Neutralization of TGF-beta by anti-TGF-beta antibody attenuates kidney hypertrophy and the enhanced extracellular matrix gene expression in STZinduced diabetic mice. Diabetes 1996;45:522-30.[Abstract]
- Brundel BJ,Van Gelder IC, Henning RH et al. Gene expression of proteins influencing the calcium homeostasis in patients with persistent and paroxysmal atrial fibrillation. Cardiovasc Res 1999;42:443-54.[Abstract/Free Full Text]
- Largo R., Gomez-Garre D., Soto K. et al. Angiotensin-converting enzyme is upregulated in the proximal tubules of rats with intense proteinuria. Hypertension 1999;33:732-9.[Abstract/Free Full Text]
- Morrissey JJ, Klahr S. Effect of AT2 receptor blockade on the pathogenesis of renal fibrosis. Am J Physiol 1999;276(1 Pt 2):F39-F45.[Web of Science][Medline]
[Order article via Infotrieve]
- Stoneking BJ, Hunley TE, Nishimura H. et al. Renal angiotensin converting enzyme promotes renal damage during ureteral obstruction. J Urol 1998;160(3 Pt 2):1070-4.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Tamaki K., Okuda S., Miyazono K., Nakayama M., Fujishima M. Matrix-associated latent TGF-beta with latent TGF-beta binding protein in the progressive process in adriamycin-induced nephropathy. Lab Invest 1995;73:81-9.[Web of Science][Medline]
[Order article via Infotrieve]
- Tamaki K., Okuda S., Ando T., Iwamoto T., Nakayama M., Fujishima M. TGF-beta 1 in glomerulosclerosis and interstitial fibrosis of adriamycin nephropathy. Kidney Int 1994;45:525-36.[Web of Science][Medline]
[Order article via Infotrieve]
Journal of Renin-Angiotensin-Aldosterone System, Vol. 4, No. 1,
38-42 (2003)
DOI: 10.3317/jraas.2003.006
 CiteULike  Complore  Connotea  Del.icio.us  Digg  Reddit  Technorati  Twitter What's this?
This article has been cited by other articles:
|
|
|
|
 
A. B. Kramer, M. M. van Timmeren, T. A. Schuurs, V. S. Vaidya, J. V. Bonventre, H. van Goor, and G. Navis
Reduction of proteinuria in adriamycin-induced nephropathy is associated with reduction of renal kidney injury molecule (Kim-1) over time
Am J Physiol Renal Physiol,
May 1, 2009;
296(5):
F1136 - F1145.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
