The renal retinoid system: time-dependent activation in experimental glomerulonephritis.
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.
Department of Nephrology, University Hospital, University of Heidelberg, Bergheimer Strasse 56a, D-69115 Heidelberg, Germany.
Sabine
S
Liebler
Birgit
B
Uberschär
Helen
H
Kübert
Stefanie
S
Brems
Anna
A
Schnitger
Miki
M
Tsukada
Christos C
CC
Zouboulis
Eberhard
E
Ritz
Jürgen
J
Wagner
D000429:Alcohol Oxidoreductases / Q000235:genetics / Q000378:metabolism; D000445:Aldehyde Oxidoreductases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure; D002452:Cell Count; D000072467:Cytochrome P450 Family 2; D005921:Glomerulonephritis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015474:Isotretinoin / Q000494:pharmacology; D007678:Kidney Glomerulus / Q000378:metabolism* / Q000473:pathology; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism; D050697:Retinal Dehydrogenase; D047488:Retinoid X Receptors; D012176:Retinoids / Q000097:blood / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D012176:Retinoids; D014157:Transcription Factors; D000429:Alcohol Oxidoreductases; C022520:retinol dehydrogenase; C504568:Cyp2d1 protein, rat; D000072467:Cytochrome P450 Family 2; D000445:Aldehyde Oxidoreductases; D050697:Retinal Dehydrogenase; D015474:Isotretinoin