The renal retinoid system: time-dependent activation in experimental glomerulonephritis

Am J Physiol Renal Physiol. 2004 Mar;286(3):F458-65. doi: 10.1152/ajprenal.00173.2003. Epub 2003 Oct 28.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcohol Oxidoreductases / genetics
  • Alcohol Oxidoreductases / metabolism
  • Aldehyde Oxidoreductases / genetics
  • Aldehyde Oxidoreductases / metabolism
  • Animals
  • Blood Pressure
  • Cell Count
  • Cytochrome P450 Family 2
  • Glomerulonephritis / genetics
  • Glomerulonephritis / metabolism*
  • Glomerulonephritis / pathology
  • Isotretinoin / pharmacology
  • Kidney Glomerulus / metabolism*
  • 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
  • Retinoids / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • RNA, Messenger
  • Receptors, Retinoic Acid
  • Retinoid X Receptors
  • Retinoids
  • Transcription Factors
  • Alcohol Oxidoreductases
  • retinol dehydrogenase
  • Cyp2d1 protein, rat
  • Cytochrome P450 Family 2
  • Aldehyde Oxidoreductases
  • Retinal Dehydrogenase
  • Isotretinoin