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| Home > Publications database > A comprehensive transcriptome characterization of individual nuclear receptor pathways in the human small intestine. |
| Journal Article | DKFZ-2024-02211 |
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2024
National Acad. of Sciences
Washington, DC
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Please use a persistent id in citations: doi:10.1073/pnas.2411189121
Abstract: Nuclear receptors (NRs) are widely expressed transcription factors that bind small, lipophilic compounds and regulate diverse biological processes. In the small intestine, NRs are known to act as sensors that control transcriptional responses to endogenous and exogenous signals, yet their downstream effects have not been characterized extensively. Here, we investigate the activation of six different NRs individually in human intestinal organoids using small molecules agonists. We observe changes in key enterocyte functions such as lipid, glucose, and amino acid absorption, the regulation of electrolyte balance, and drug metabolism. Our findings reinforce PXR, LXR, FXR, and PPARĪ± as regulators of lipid absorption. Furthermore, known hepatic effects of AHR and VDR activation were recapitulated in the human small intestine. Finally, we identify unique target genes for intestinal PXR activation (ERG28, TMEM97, and TM7SF2), LXR activation (RAB6B), and VDR activation (CA12). This study provides an unbiased and comprehensive transcriptomic description of individual NR pathways in the human small intestine. By gaining a deeper understanding of the effects of individual NRs, we might better harness their pharmacological and therapeutic potential.
Keyword(s): Humans (MeSH) ; Intestine, Small: metabolism (MeSH) ; Receptors, Cytoplasmic and Nuclear: metabolism (MeSH) ; Receptors, Cytoplasmic and Nuclear: genetics (MeSH) ; Transcriptome (MeSH) ; Receptors, Calcitriol: metabolism (MeSH) ; Receptors, Calcitriol: genetics (MeSH) ; Liver X Receptors: metabolism (MeSH) ; Liver X Receptors: genetics (MeSH) ; Liver X Receptors: agonists (MeSH) ; Organoids: metabolism (MeSH) ; Signal Transduction (MeSH) ; Lipid Metabolism: genetics (MeSH) ; Enterocytes: metabolism (MeSH) ; Pregnane X Receptor: metabolism (MeSH) ; Pregnane X Receptor: genetics (MeSH) ; Gene Expression Regulation: drug effects (MeSH) ; lipid absorption ; nuclear receptors ; organoids ; small intestine ; Receptors, Cytoplasmic and Nuclear ; Receptors, Calcitriol ; Liver X Receptors ; VDR protein, human ; Pregnane X Receptor
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