LOSS OF RETINOID RECEPTORS RAR-A AND RXR-A DURING MONOCROTALIN/LIPOPOLYSACCHARIDE-INDUCED RENAL TOXICITY IS TISSUE FACTOR DEPENDENT | ||||
| Al-Azhar Journal of Pharmaceutical Sciences | ||||
| Article 8, Volume 46, Issue 2 - Serial Number 46, September 2012, Page 100-114 PDF (728.29 K) | ||||
| Document Type: Original Article | ||||
| DOI: 10.21608/ajps.2012.7139 | ||||
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| Author | ||||
| Mohamed Abdel-Bakky | ||||
| Faculty of Pharmacy, Al-Azhar University, Nasr City, Cairo, Egypt | ||||
| Abstract | ||||
| Retinoic acid receptors (RARs) are ligand-controlled transcription factors that function as heterodimers with retinoid X receptors (RXRs) to regulate cell growth, differentiation, survival and death. Due to their regulatory potential, these nuclear receptors (NRs) are major drug targets for a variety of pathologies, including cancer and metabolic diseases. We reported earlier the involvement of tissue factor (TF) in the release of retinoid receptors RAR-α and RXR-α as accumulated lipid droplet during monocrotaline/lipopolysaccharide (MCT/LPS)-liver injury in mice. In the kidney, little is known about the localization and the functional significance of RXR-a and RAR- a. In this study, we were able to find RXR-a receptor in distal, proximal tubules as well as glomeruli of mice kidney. In addition, RAR-a expression is restricted to the glomeruli and endothelial cells of the blood vessels. Furthermore, following MCT/LPS co-treatment, we found the translocation of RXR-a from basolateral into the apical site in the distal tubules and collecting duct along with downregulation of glomerular RAR-a. This study reports the involvement of TF in the tubular translocation of retinoid receptor RXR-α and the glomerular downregulation of RAR-a during MCT/LPS-renal injury. The fact that TF antisense oligonucleotides (TF-AS ODN) treatment not only down-regulated TF but also obliterated the tubular translocation of RXR-a and glomerular RAR-a downregulation points towards TF being an important regulatory molecule for renal RAR-α and RXR-α. | ||||
| Keywords | ||||
| Tissue Factor; retinoic acid receptor alpha; retinoid X receptor alpha; tissue factor antisense oligodeoxynucleotides | ||||
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