دورية أكاديمية
Interleukin-1β Suppresses Gastrin via Primary Cilia and Induces Antral Hyperplasia
| العنوان: | Interleukin-1β Suppresses Gastrin via Primary Cilia and Induces Antral Hyperplasia |
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| المؤلفون: | Ding, L., Sontz, E.A., Saqui-Salces, M., Merchant, J.L. |
| المساهمون: | Department of Medicine-Gastroenterology, University of Arizona |
| المصدر: | Cellular and Molecular Gastroenterology and Hepatology |
| بيانات النشر: | Elsevier Inc. |
| سنة النشر: | 2021 |
| المجموعة: | The University of Arizona: UA Campus Repository |
| مصطلحات موضوعية: | Gastric Cancer, Hedgehog Signaling, Helicobacter, IFN-γ, KIF3A |
| الوصف: | Background & Aims: Helicobacter pylori infection in humans typically begins with colonization of the gastric antrum. The initial Th1 response occasionally coincides with an increase in gastrin secretion. Subsequently, the gastritis segues to chronic atrophic gastritis, metaplasia, dysplasia and distal gastric cancer. Despite these well characterized clinical events, the link between inflammatory cytokines and non-cardia gastric cancer remains difficult to study in mouse models. Prior studies have demonstrated that overexpression of the Hedgehog (HH) effector GLI2 induces loss of gastrin (atrophy) and antral hyperplasia. To determine the link between specific cytokines, HH signaling and pre-neoplastic changes in the gastric antrum. Methods: Mouse lines were created to conditionally direct IL1β or IFN-γ to the antrum using the Gastrin-CreERT2 and Tet activator. Primary cilia, which transduces HH signaling, on G cells were disrupted by deleting the ciliary motor protein KIF3a. Phenotypic changes were assessed by histology and western blots. A subclone of GLUTag enteroendocrine cells selected for gastrin expression and the presence of primary cilia was treated with recombinant SHH, IL1β or IFN-γ with or without kif3a siRNA. Results: IFN-γ increased gastrin and induced antral hyperplasia. However, antral expression of IL1β suppressed tissue and serum gastrin, while also inducing antral hyperplasia. IFN-γ treatment of GLUTAg cells suppressed GLI2 and induced gastrin, without affecting cilia length. By contrast, IL1β treatment doubled primary cilia length, induced GLI2 and suppressed gastrin gene expression. Knocking down kif3a in GLUTAg cells mitigated SHH or IL1β suppression of gastrin. Conclusions: Overexpression of IL1β in the antrum was sufficient to induce antral hyperplasia coincident with suppression of gastrin via primary cilia. ORCID: #0000-0002-6559-8184 © 2021 The Authors ; Open access journal ; This item from the UA Faculty Publications collection is made available by the University of Arizona with ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 2352-345X 33347972 |
| العلاقة: | Ding, L., Sontz, E. A., Saqui-Salces, M., & Merchant, J. L. (2021). Interleukin-1β suppresses gastrin via primary cilia and induces antral hyperplasia. Cellular and Molecular Gastroenterology and Hepatology, 11(5), 1251-1266.; http://hdl.handle.net/10150/659934Test; Cellular and Molecular Gastroenterology and Hepatology |
| DOI: | 10.1016/j.jcmgh.2020.12.008 |
| الإتاحة: | https://doi.org/10.1016/j.jcmgh.2020.12.008Test http://hdl.handle.net/10150/659934Test |
| حقوق: | Copyright © 2021 The Authors. Published by Elsevier Inc. on behalf of the AGA Institute. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0Test/). ; https://creativecommons.org/licenses/by-nc-nd/4.0Test/ |
| رقم الانضمام: | edsbas.A5636DB1 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 2352345X 33347972 |
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| DOI: | 10.1016/j.jcmgh.2020.12.008 |