Academic Journal
Opposing roles of nuclear receptor HNF4α isoforms in colitis and colitis-associated colon cancer
| العنوان: | Opposing roles of nuclear receptor HNF4α isoforms in colitis and colitis-associated colon cancer |
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| المؤلفون: | Karthikeyani Chellappa, Poonamjot Deol, Jane R Evans, Linh M Vuong, Gang Chen, Nadege Briançon, Eugene Bolotin, Christian Lytle, Meera G Nair, Frances M Sladek |
| المصدر: | eLife, Vol 5 (2016) |
| بيانات النشر: | eLife Sciences Publications Ltd, 2016. |
| سنة النشر: | 2016 |
| المجموعة: | LCC:Medicine LCC:Science LCC:Biology (General) |
| مصطلحات موضوعية: | nuclear receptor, alternative promoters, exon swap mice, colonic crypts, colitis, colon cancer, Medicine, Science, Biology (General), QH301-705.5 |
| الوصف: | HNF4α has been implicated in colitis and colon cancer in humans but the role of the different HNF4α isoforms expressed from the two different promoters (P1 and P2) active in the colon is not clear. Here, we show that P1-HNF4α is expressed primarily in the differentiated compartment of the mouse colonic crypt and P2-HNF4α in the proliferative compartment. Exon swap mice that express only P1- or only P2-HNF4α have different colonic gene expression profiles, interacting proteins, cellular migration, ion transport and epithelial barrier function. The mice also exhibit altered susceptibilities to experimental colitis (DSS) and colitis-associated colon cancer (AOM+DSS). When P2-HNF4α-only mice (which have elevated levels of the cytokine resistin-like β, RELMβ, and are extremely sensitive to DSS) are crossed with Retnlb-/- mice, they are rescued from mortality. Furthermore, P2-HNF4α binds and preferentially activates the RELMβ promoter. In summary, HNF4α isoforms perform non-redundant functions in the colon under conditions of stress, underscoring the importance of tracking them both in colitis and colon cancer. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2050-084X 61409596 |
| Relation: | https://elifesciences.org/articles/10903; https://doaj.org/toc/2050-084X |
| DOI: | 10.7554/eLife.10903 |
| URL الوصول: | https://doaj.org/article/8567af03de6140959642cdc4b36f09cb |
| رقم الانضمام: | edsdoj.8567af03de6140959642cdc4b36f09cb |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 2050084X 61409596 |
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| DOI: | 10.7554/eLife.10903 |