Tissue barriers, 2016-07, Vol.4 (3), p.e1214038-e1214038
2016
Volltextzugriff (PDF)
Details
- Autor(en) / Beteiligte
- Titel
- Claudin-based barrier differentiation in the colonic epithelial crypt niche involves Hopx/Klf4 and Tcf7l2/Hnf4-α cascades
- Ist Teil von
- Tissue barriers, 2016-07, Vol.4 (3), p.e1214038-e1214038
- Ort / Verlag
- United States: Taylor & Francis
- Erscheinungsjahr
- 2016
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2168-8362, 2168-8370eISSN: 2168-8370DOI: 10.1080/21688370.2016.1214038Titel-ID: cdi_informaworld_taylorfrancis_310_1080_21688370_2016_1214038
- Format
- –
- Schlagworte
- Animals, Cell Differentiation, claudins, Claudins - genetics, Claudins - metabolism, Colon - cytology, Colon - metabolism, colonic crypts, Gene Expression Regulation, Developmental, Hepatocyte Nuclear Factor 4 - genetics, Hepatocyte Nuclear Factor 4 - metabolism, Homeodomain Proteins - genetics, Homeodomain Proteins - metabolism, intestinal barrier, Intestinal Mucosa - cytology, Intestinal Mucosa - metabolism, Kruppel-Like Factor 4, Kruppel-Like Transcription Factors - genetics, Kruppel-Like Transcription Factors - metabolism, Male, Mice, Mice, Inbred C57BL, Research Paper, Stem Cell Niche, Transcription Factor 7-Like 2 Protein - genetics, Transcription Factor 7-Like 2 Protein - metabolism