ArticleTissue barriers
Claudin-based barrier differentiation in the colonic epithelial crypt niche involves Hopx/Klf4 and Tcf7l2/Hnf4-α cascades.
Article in Tissue barriers. 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.
- Article
- Claudin-23 reshapes epithelial tight junction architecture to regulate barrier function.Nature communications · 2023Article
- The HOPX and BLBP landscape and gliogenic regions in developing human brain.Journal of anatomy · 2023Article
- Article
- The role of HOPX in normal tissues and tumor progression.Bioscience reports · 2020Review
- NCoR1 Protects Mice From Dextran Sodium Sulfate-Induced Colitis by Guarding Colonic Crypt Cells From Luminal Insult.Cellular and molecular gastroenterology and hepatology · 2020Article
- Layered defense: how mucus and tight junctions seal the intestinal barrier.Journal of molecular medicine (Berlin, Germany) · 2017Review
- Involvement of CRF2 signaling in enterocyte differentiation.World journal of gastroenterology · 2017Article
- Disruption of the epithelial barrier during intestinal inflammation: Quest for new molecules and mechanisms.Biochimica et biophysica acta. Molecular cell research · 2017Review
- Intestinal epithelial claudins: expression and regulation in homeostasis and inflammation.Annals of the New York Academy of Sciences · 2017Review
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Colonic enterocytes form a rapidly renewing epithelium and barrier to luminal antigens. During renewal, coordinated expression of the claudin family of genes is vital to maintain the epithelial barrier. Disruption of this process contributes to barrier compromise and mucosal inflammatory diseases. However, little is known about the regulation of this critical aspect of epithelial cell differentiation. In order to identify claudin regulatory factors we utilized high-throughput gene microarrays and correlation analyses. We identified complex expression gradients for the transcription factors Hopx, Hnf4a, Klf4 and Tcf7l2, as well as 12 claudins, during differentiation. In vitro confirmatory methods identified 2 pathways that stimulate claudin expression; Hopx/Klf4 activation of Cldn4, 7 and 15, and Tcf7l2/Hnf4a up-regulation of Cldn23. Chromatin immunoprecipitation confirmed a Tcf7l2/Hnf4a/Claudin23 cascade. Furthermore, Hnf4a conditional knockout mice fail to induce Cldn23 during colonocyte differentiation. In conclusion, we report a comprehensive screen of colonic claudin gene expression and discover spatiotemporal Hopx/Klf4 and Tcf7l2/Hnf4a signaling as stimulators of colonic epithelial barrier differentiation.
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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.