ArticleLiver international : official journal of the International Association for the Study of the Liver2012
Gene-specific alterations of hepatic gene expression by ligand activation or hepatocyte-selective inhibition of retinoid X receptor-α signalling during inflammation.
Article in Liver international : official journal of the International Association for the Study of the Liver, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 5 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
5 citing papers in PubMed, 6 citations in OpenAlex.
- Phytosterols Synergize With Endotoxin to Augment Inflammation in Kupffer Cells but Alone Have Limited Direct Effect on Hepatocytes.JPEN. Journal of parenteral and enteral nutrition · 2018Article
- Inhibition of ileal bile acid uptake protects against nonalcoholic fatty liver disease in high-fat diet-fed mice.Science translational medicine · 2016Article
- Inflammation-associated upregulation of the sulfated steroid transporter Slc10a6 in mouse liver and macrophage cell lines.Hepatology research : the official journal of the Japan Society of Hepatology · 2016Article
- Impaired bile acid handling and aggravated liver injury in mice expressing a hepatocyte-specific RXRα variant lacking the DNA-binding domain.Journal of hepatology · 2014Article
- Article
Corrections and comments
- Erratum issuedWan, Yvonne Yu-Jie [corrected to Wan, Yu-Jui Yvonne]
Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundInflammation leads to transcriptional downregulation of many hepatic genes, particularly those activated by retinoid X receptor-α (RXRα) heterodimers. Inflammation-mediated reduction of nuclear RXRα levels is a main factor in reduced nuclear receptor (NR)-regulated hepatic gene expression, eventually leading to cholestasis and liver damage.
aimTo investigate roles for RXRα in hepatic gene expression during inflammation, using two complementary mouse models: ligand activation of RXRα, and in mice expressing hepatocyte-specific expression of RXRα missing its DNA-binding domain (DBD; hs-RxrαΔex4(-/-) ).
methodsTo activate RXRα, mice were gavage-fed with LG268 or vehicle for 5 days. To inhibit RXRα function, hs-RxrαΔex4(-/-) mice were used. All mice were injected intraperitoneally with lipopolysaccharides (LPS) or saline for 16 h prior to analysis of hepatic RNA, protein and NR-DNA binding.
resultsLG268 treatment attenuated the LPS-mediated reductions of several RXRα-regulated genes, coinciding with maintained RXRα occupancy in both Bsep and Ostβ promoters. Lacking full hepatocyte RXRα function (hs-RxrαΔex4(-/-) mice) led to enhancement of LPS-mediated changes in gene expression, but surprisingly, maintenance of RNA levels of some RXRα-regulated genes. Investigations revealed that hs-RxrαΔex4(-/-) hepatocytes expressed an internally truncated, approximately 44 kDa, RXRα-form. DNA-binding capacity of NR heterodimers was equivalent in wild-type and hs-RxrαΔex4(-/-) livers, but reduced by LPS in both. Chromatin immunoprecipitation quantitative PCR revealed that RXRα occupancy to the Bsep RXRα:Farnesoid X Receptor site was reduced, but not absent, in hs-RxrαΔex4(-/-) livers.
conclusionsThere are differential regulatory roles for hepatic RXRα, both in basal and inflammatory states, suggesting new and complex multidomain roles for RXRα in regulating hepatic gene expression. Moreover, there is an unexpected non-obligate role for the DBD of RXRα.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.