ArticleInflammatory bowel diseases2020
All-trans Retinoic Acid Counteracts Diarrhea and Inhibition of Downregulated in Adenoma Expression in Gut Inflammation.
Article in Inflammatory bowel diseases, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 18 citations in OpenAlex.
- Retinoic acid in health and disease.Signal transduction and targeted therapy · 2026Review
- Effects of All-Trans Retinoic Acid on Ovarian Development, Lipid Metabolism, Nutritional Quality, and Gut Microbiota of Female Chinese Mitten Crab During Fattening Period.International journal of molecular sciences · 2026Article
- ATRA-mediated RAR-α activation attenuates acrylamide-induced testicular toxicity.Scientific reports · 2026Article
- Autophagy Regulates Putative Anion Transporter 1 Expression in Intestinal Epithelial Cells.Journal of cellular and molecular medicine · 2025Article
- Dexamethasone Upregulates the Expression of the Human SLC26A3 (DRA, Down-Regulated in Adenoma) Transporter (an IBD Susceptibility Gene) in Intestinal Epithelial Cells and Attenuates Gut Inflammation.Inflammatory bowel diseases · 2025Article
- Isobutyrate Confers Resistance to Inflammatory Bowel Disease through Host-Microbiota Interactions in Pigs.Research (Washington, D.C.) · 2025Article
- Bicarbonate secretion and acid/base sensing by the intestine.Pflugers Archiv : European journal of physiology · 2024Review
- Multiple Regulatory Signals and Components in the Modulation of Bicarbonate Transporters.Pharmaceutics · 2024Review
- Article
- DRAwing Conclusions About the Basis of Diarrhea in Inflammatory Bowel Disease.Digestive diseases and sciences · 2020Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundIntestinal epithelial apical membrane Cl-/HCO3- exchanger DRA (downregulated in adenoma, SLC26A3) has emerged as an important therapeutic target for diarrhea, emphasizing the potential therapeutic role of agents that upregulate DRA. All-trans retinoic acid (ATRA), a key vitamin A metabolite, was earlier shown by us to stimulate DRA expression in intestinal epithelial cells. However, its role in modulating DRA in gut inflammation has not been investigated.
aimsOur aim was to analyze the efficacy of ATRA in counteracting inflammation-induced decrease in DRA in vitro and in vivo.
methodsInterferon-γ (IFN-γ)-treated Caco-2 cells and dextran sulfate sodium (DSS)-treated C57BL/6J mice served as in vitro and in vivo models of gut inflammation, respectively. The effect of ATRA on IFN-γ-mediated inhibition of DRA function, expression, and promoter activity were elucidated. In the DSS colitis model, diarrheal phenotype, cytokine response, in vivo imaging, myeloperoxidase activity, and DRA expression were measured in the distal colon.
resultsAll-trans retinoic acid (10 μM, 24 h) abrogated IFN-γ (30 ng/mL, 24 h)-induced decrease in DRA function, expression, and promoter activity in Caco-2 cells. All-trans retinoic acid altered IFN-γ signaling via blocking IFN-γ-induced tyrosine phosphorylation of STAT-1. All-trans retinoic acid cotreatment (1 mg/kg BW, i.p. daily) of DSS-treated mice (3% in drinking water for 7 days) alleviated colitis-associated weight loss, diarrheal phenotype, and induction of IL-1β and CXCL1 and a decrease in DRA mRNA and protein levels in the colon.
conclusionOur data showing upregulation of DRA under normal and inflammatory conditions by ATRA demonstrate a novel role of this micronutrient in alleviating IBD-associated diarrhea.
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