Expression of retinoic acid receptor and retinoid X receptor subtypes in rat liver cells: Implications for retinoid signalling in parenchymal, endothelial, Kupffer and stellate cells

Ulven, Stine Marie; Natarajan, Vasanti; Holven, Kirsten B.; Løvdal, Torunn; Berg, Trond; Blomhoff, Rune

doi:10.1016/s0171-9335(98)80078-2

Cited by 39 publications

(26 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As alpha isoform of both RAR and RXR is the dominant isoform in liver cells (Abdel-Bakky et al 2010;AbdelBakky et al 2011;Ulven et al 1998;Mezaki et al 2009;Mezaki et al 2007), the current study focused on the investigation of the potential role of RXR-α and RAR-α in MTXinduced hepatic toxicity. In our study, RXR-α was constitutively expressed in the parenchymal cells and pericentral hepatocytes of control rat .…”

Section: Discussionmentioning

confidence: 99%

All-trans retinoic acid mitigates methotrexate-induced liver injury in rats; relevance of retinoic acid signaling pathway

Ewees

Abdelghany

Abdel-Aziz

et al. 2015

Naunyn-Schmiedeberg's Arch Pharmacol

View full text Add to dashboard Cite

Methotrexate (MTX) is a widely used drug for treatment of rheumatic and autoimmune diseases as well as different types of cancer. One of the major side effects of MTX is hepatotoxicity. Retinoid receptors, including retinoid X receptor (RXR), and retinoic acid receptor (RAR) are vitamin A receptors that are highly expressed in the liver and regulate important physiological processes through regulation of different genes. In this study, we investigated the effect of MTX on RXR-α and RAR-α expression in the liver and the potential protective effects of all-trans retinoic acid (ATRA) in MTX-induced hepatotoxicity. Rats were randomly divided into five groups: The rates were treated with saline, DMSO, MTX (20 mg/kg/IP; single dose), ATRA (7.5 mg/kg/day, I.P), or MTX and ATRA. Rats were killed 24 h after the last ATRA injection. The liver tissues were dissected out, weighed, and subjected to histological, immunohistochemical, and biochemical examinations. Our results demonstrated that treatment with MTX resulted in significant decrease in reduced glutathione (GSH) content and superoxide dismutase (SOD) activity, with concomitant increase in ALT, AST, and MDA levels. In addition, MTX markedly downregulated the expression of both RXR-α and RAR-α, and changed the appearance of RXR-α to be very small speckled droplets. Treatment with ATRA significantly ameliorated MTX-induced effects on GSH, ALT, and MDA. Moreover, ATRA administration increased the expression and nuclear translocation of RXR-α in rat hepatocytes. In conclusion, our study revealed, for the first time, that retinoid receptors may play an important role in the MTX-induced hepatotoxicity.

show abstract

Section: Discussionmentioning

confidence: 99%

All-trans retinoic acid mitigates methotrexate-induced liver injury in rats; relevance of retinoic acid signaling pathway

Ewees

Abdelghany

Abdel-Aziz

et al. 2015

Naunyn-Schmiedeberg's Arch Pharmacol

View full text Add to dashboard Cite

show abstract

“…These receptors are members of the nuclear hormone receptor superfamily (659). In the presence of their cognate ligands, they translocate to the nucleus and act as transcription factors.…”

Section: Biology Of Nuclear Receptorsmentioning

confidence: 99%

Hepatic Stellate Cells: Protean, Multifunctional, and Enigmatic Cells of the Liver

Friedman

2008

Physiological Reviews

2,423

2,549

View full text Add to dashboard Cite

The hepatic stellate cell has surprised and engaged physiologists, pathologists, and hepatologists for over 130 years, yet clear evidence of its role in hepatic injury and fibrosis only emerged following the refinement of methods for its isolation and characterization. The paradigm in liver injury of activation of quiescent vitamin A-rich stellate cells into proliferative, contractile, and fibrogenic myofibroblasts has launched an era of astonishing progress in understanding the mechanistic basis of hepatic fibrosis progression and regression. But this simple paradigm has now yielded to a remarkably broad appreciation of the cell's functions not only in liver injury, but also in hepatic development, regeneration, xenobiotic responses, intermediary metabolism, and immunoregulation. Among the most exciting prospects is that stellate cells are essential for hepatic progenitor cell amplification and differentiation. Equally intriguing is the remarkable plasticity of stellate cells, not only in their variable intermediate filament phenotype, but also in their functions. Stellate cells can be viewed as the nexus in a complex sinusoidal milieu that requires tightly regulated autocrine and paracrine cross-talk, rapid responses to evolving extracellular matrix content, and exquisite responsiveness to the metabolic needs imposed by liver growth and repair. Moreover, roles vital to systemic homeostasis include their storage and mobilization of retinoids, their emerging capacity for antigen presentation and induction of tolerance, as well as their emerging relationship to bone marrow-derived cells. As interest in this cell type intensifies, more surprises and mysteries are sure to unfold that will ultimately benefit our understanding of liver physiology and the diagnosis and treatment of liver disease.

show abstract

“…mRNA was isolated by using the MicroFast mRNA isolation kit (Invitrogen). cDNA synthesis and PCR (40 cycles) was performed as described by Ulven et al (1998). The specific primer pairs are listed in a previous report (Ulven et al, 2000).…”

Section: Mrna Isolation and Rt-pcr Analysismentioning

confidence: 99%

Quantitative axial profiles of retinoic acid in the embryonic mouse spinal cord: 9‐Cis retinoic acid only detected after all‐trans‐retinoic acid levels are super‐elevated experimentally

Ulven

Gundersen

Sakhi

et al. 2001

Developmental Dynamics

Self Cite

View full text Add to dashboard Cite

Studies using bioassays in nor-We find a bimodal distribution of all-trans retinoic acid (at-RA), the ligand for RARs, and relate this to the expression of several retinoid-synthesizing enzymes. However, we do not detect 9-cis-retinoic acid (9-cis-RA), the putative RXR ligand, in any region of the spinal cord unless retinoid levels are massively increased experimentally by gavage feeding pregnant mice with teratogenic doses of at-RA. This study provides for the first time quantitative profiles of endogenous retinoids along the axis of the developing spinal cord, thereby establishing a foundation for more definitive studies of retinoid function in the future. It sets definite limits on how much 9-cis-RA potentially is present and demonstrates that at-RA predominates over 9-cis-RA by at least 30-to 180-fold in different spinal cord regions.

show abstract

Expression of retinoic acid receptor and retinoid X receptor subtypes in rat liver cells: Implications for retinoid signalling in parenchymal, endothelial, Kupffer and stellate cells

Cited by 39 publications

References 39 publications

All-trans retinoic acid mitigates methotrexate-induced liver injury in rats; relevance of retinoic acid signaling pathway

All-trans retinoic acid mitigates methotrexate-induced liver injury in rats; relevance of retinoic acid signaling pathway

Hepatic Stellate Cells: Protean, Multifunctional, and Enigmatic Cells of the Liver

Quantitative axial profiles of retinoic acid in the embryonic mouse spinal cord: 9‐Cis retinoic acid only detected after all‐trans‐retinoic acid levels are super‐elevated experimentally

Contact Info

Product

Resources

About