ArticleInflammatory bowel diseases2012
Loss of downregulated in adenoma (DRA) impairs mucosal HCO3(-) secretion in murine ileocolonic inflammation.
Article in Inflammatory bowel diseases, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 90 citations in OpenAlex.
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- The genetics of monogenic intestinal epithelial disorders.Human genetics · 2023Review
- Human Colonoid-Myofibroblast Coculture for Study of Apical NaInternational journal of molecular sciences · 2023Article
- Role of SLC4 and SLC26 solute carriers during oxidative stress.Acta physiologica (Oxford, England) · 2022Review
- Alterations of mucosa-attached microbiome and epithelial cell numbers in the cystic fibrosis small intestine with implications for intestinal disease.Scientific reports · 2022Article
- Pathophysiological role of ion channels and transporters in gastrointestinal mucosal diseases.Cellular and molecular life sciences : CMLS · 2021Review
- A Novel Role of SLC26A3 in the Maintenance of Intestinal Epithelial Barrier Integrity.Gastroenterology · 2021Article
- Segmental differences in Slc26a3-dependent ClThe journal of physiological sciences : JPS · 2021Article
- The Role of pHFrontiers in cell and developmental biology · 2021Review
- All-trans Retinoic Acid Counteracts Diarrhea and Inhibition of Downregulated in Adenoma Expression in Gut Inflammation.Inflammatory bowel diseases · 2020Article
- Importance of SLC26 Transmembrane Anion Exchangers in Sperm Post-testicular Maturation and Fertilization Potential.Frontiers in cell and developmental biology · 2019Review
- Adenosinergic signaling inhibits oxalate transport by human intestinal Caco2-BBE cells through the AAmerican journal of physiology. Cell physiology · 2018Article
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Authors and funding
15 authors at 6 institutions in 4 countries.
Funding
Abstract
backgroundIleocolonic luminal pH has been reported to be abnormally low in inflammatory bowel disease (IBD) patients, and one of the causative factors may be reduced epithelial HCO(3)(-) secretory rate (J(HCO3)(-)). Disturbances in J(HCO3)(-) may occur due to inflammation-induced changes in the crypt and villous architecture, or due to the effect of proinflammatory cytokines on epithelial ion transporters.
methodsTo discriminate between these possibilities, the tumor necrosis factor alpha (TNF-α) overexpressing (TNF(+/ΔARE)) mouse model was chosen, which displays high proinflammatory cytokine levels in both ileum and colon, but develops only mild colonic histopathology and diarrhea. HCO(3)(-) secretion, mRNA expression, immunohistochemistry, and fluid absorptive capacity were measured in ileal and mid-colonic mucosa of TNF(+/ΔARE) and wildtype (WT) (TNF(+/+)) mice in Ussing chambers, and in anesthetized mice in vivo.
resultsThe high basal J(HCO3)(-) observed in WT ileal and mid-colonic mucosa were luminal Cl(-) -dependent and strongly decreased in TNF(+/ΔARE) mice. Downregulated in adenoma (DRA) mRNA and protein expression was strongly decreased in TNF(+/ΔARE) ileocolon, whereas cystic fibrosis transmembrane conductance regulator (CFTR), Na(+) /H(+) exchanger 3 (NHE3), Na(+) /HCO(3)(-) cotransporter (NBC), and epithelial sodium channel (ENaC) expression was not significantly altered. This indicates that the severe defect in ileocolonic J(HCO3)(-) was due to DRA downregulation. Fluid absorption was severely depressed in the ileum but only mildly affected in the mid-distal colon, preventing the development of overt diarrhea.
conclusionsEven mild ileocolonic inflammation may result in a decrease of epithelial HCO(3)(-) secretion, which may contribute to alterations in surface pH, intestinal flora, and mucus barrier properties.
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