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Am J Physiol Renal Physiol ; 286(3): F458-65, 2004 Mar.
Article in English | MEDLINE | ID: mdl-14583434

ABSTRACT

Retinoids reduce renal damage in rat experimental glomerulonephritis. It is unknown, however, how local and systemic retinoid pathways respond to renal injury. We used a rat model of artificially induced acute anti-Thy1.1-nephritis (THY-GN). We examined the extrarenal and glomerular expression of the retinol (RoDH) and retinal (RalDH) dehydrogenases 1 and 2 as well as the expression of the retinoic acid (RAR) and retinoid X (RXR) receptor subtypes alpha, beta, and gamma. Furthermore, we investigated serum and glomerular retinoid concentration patterns. On days 3, 7, and 14, we compared nonnephritic rats (control group; CON) to THY-GN rats with respect to systolic blood pressure and glomerular cell count per cross section. Systolic blood pressure and glomerular cell count were significantly higher in THY-GN rats on days 7 and 14 (P < 0.001). We found a 60% reduction in expression levels for retinoid receptors and dehydrogenases in nephritic glomeruli on day 3, but a threefold increase on day 7 (P < 0.001 vs. CON). The same applies to RAR alpha protein. Hepatic expression of retinoid receptors was not influenced. On day 14, glomerular expression levels for retinoid receptors and retinoid-metabolizing enzymes had returned to a normal level, glomerular cell count being still increased. Administering 13-cis retinoic acid (isotretinoin) lowered blood pressure and glomerular cell count in nephritic rats but failed to influence the glomerular expression of retinoid receptors or retinoid-metabolizing enzymes. Our data document a stimulation of glomerular retinoid-synthesizing enzymes and expression of retinoid receptors in the early repair phase of THY-GN, suggesting activation of this system in acute renal disease.


Subject(s)
Glomerulonephritis/metabolism , Kidney Glomerulus/metabolism , Retinoids/metabolism , Alcohol Oxidoreductases/genetics , Alcohol Oxidoreductases/metabolism , Aldehyde Oxidoreductases/genetics , Aldehyde Oxidoreductases/metabolism , Animals , Blood Pressure , Cell Count , Cytochrome P450 Family 2 , Glomerulonephritis/genetics , Glomerulonephritis/pathology , Isotretinoin/pharmacology , Kidney Glomerulus/pathology , Kinetics , Liver/metabolism , Male , RNA, Messenger/metabolism , Rats , Rats, Wistar , Receptors, Retinoic Acid/genetics , Receptors, Retinoic Acid/metabolism , Retinal Dehydrogenase , Retinoid X Receptors , Retinoids/blood , Transcription Factors/genetics , Transcription Factors/metabolism
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