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Histopathological features of the proper gastric glands in FVB/N-background mice carrying constitutively-active aryl-hydrocarbon receptor
BACKGROUND: Aryl-hydrocarbon receptor (AhR) is a multiple ligand-activated transcription factor that has important roles in xenobiotic, physiological, or pathological functions. Transgenic mice systemically expressing constitutively-active AhR (CA-AhR) have been created to mimic activated AhR signal...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6588904/ https://www.ncbi.nlm.nih.gov/pubmed/31226941 http://dx.doi.org/10.1186/s12876-019-1009-x |
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author | Dantsuka, Ai Ichii, Osamu Hanberg, Annika Elewa, Yaser Hosny Ali Otsuka-Kanazawa, Saori Nakamura, Teppei Kon, Yasuhiro |
author_facet | Dantsuka, Ai Ichii, Osamu Hanberg, Annika Elewa, Yaser Hosny Ali Otsuka-Kanazawa, Saori Nakamura, Teppei Kon, Yasuhiro |
author_sort | Dantsuka, Ai |
collection | PubMed |
description | BACKGROUND: Aryl-hydrocarbon receptor (AhR) is a multiple ligand-activated transcription factor that has important roles in xenobiotic, physiological, or pathological functions. Transgenic mice systemically expressing constitutively-active AhR (CA-AhR) have been created to mimic activated AhR signaling in vivo. However, their detailed histopathological features are unclear. In the present study, we generated CA-AhR-expressing FVB/N mice (FVB-CA-AhR mice) and clarified their phenotypes in detail. METHODS: Male and female FVB-CA-AhR and wild-type mice were histopathologically examined from 6 to 33 weeks of age. RESULTS: Among the systemic organs, only the stomachs in FVB-CA-AhR mice showed pathological changes including cystic structures beneath the serosa; in addition, stomach weights increased with age. Histopathologically, cystic structures and alcian blue-positive metaplasia were observed in the mucosa of the proper gastric glands, and these two histometric parameters were positively correlated. Furthermore, proliferating cells shifted from the isthmus to the base of the glands, and parietal cells decreased. Age-related histopathological changes were clearer in females than in males. Importantly, in FVB-CA-AhR mice, intramucosal cysts developed as extramucosal cysts beneath the serosa, penetrating the lamina muscularis mucosae and the muscularis propria. Their incidence reached 100% in 28-week-old male mice and 33-week-old female mice. Extramucosal cysts contained alcian blue-, Griffonia simplicifolia lectin II-, or trefoil factor 2-positive cells, suggesting a stomach origin for the cysts and spasmolytic polypeptide-expressing metaplasia-like lesions. CONCLUSIONS: Disease onset occurred earlier in FVB-CA-AhR mice than previously reported in C57BL/6-derived CA-AhR mice. Importantly, the histopathological features were partly similar with gastritis cystica profunda in humans and animals. Excessive activation of AhR signaling aggravated abnormalities in the gastric mucosa and were affected by both genetic- and sex-related factors. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12876-019-1009-x) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-6588904 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-65889042019-07-08 Histopathological features of the proper gastric glands in FVB/N-background mice carrying constitutively-active aryl-hydrocarbon receptor Dantsuka, Ai Ichii, Osamu Hanberg, Annika Elewa, Yaser Hosny Ali Otsuka-Kanazawa, Saori Nakamura, Teppei Kon, Yasuhiro BMC Gastroenterol Research Article BACKGROUND: Aryl-hydrocarbon receptor (AhR) is a multiple ligand-activated transcription factor that has important roles in xenobiotic, physiological, or pathological functions. Transgenic mice systemically expressing constitutively-active AhR (CA-AhR) have been created to mimic activated AhR signaling in vivo. However, their detailed histopathological features are unclear. In the present study, we generated CA-AhR-expressing FVB/N mice (FVB-CA-AhR mice) and clarified their phenotypes in detail. METHODS: Male and female FVB-CA-AhR and wild-type mice were histopathologically examined from 6 to 33 weeks of age. RESULTS: Among the systemic organs, only the stomachs in FVB-CA-AhR mice showed pathological changes including cystic structures beneath the serosa; in addition, stomach weights increased with age. Histopathologically, cystic structures and alcian blue-positive metaplasia were observed in the mucosa of the proper gastric glands, and these two histometric parameters were positively correlated. Furthermore, proliferating cells shifted from the isthmus to the base of the glands, and parietal cells decreased. Age-related histopathological changes were clearer in females than in males. Importantly, in FVB-CA-AhR mice, intramucosal cysts developed as extramucosal cysts beneath the serosa, penetrating the lamina muscularis mucosae and the muscularis propria. Their incidence reached 100% in 28-week-old male mice and 33-week-old female mice. Extramucosal cysts contained alcian blue-, Griffonia simplicifolia lectin II-, or trefoil factor 2-positive cells, suggesting a stomach origin for the cysts and spasmolytic polypeptide-expressing metaplasia-like lesions. CONCLUSIONS: Disease onset occurred earlier in FVB-CA-AhR mice than previously reported in C57BL/6-derived CA-AhR mice. Importantly, the histopathological features were partly similar with gastritis cystica profunda in humans and animals. Excessive activation of AhR signaling aggravated abnormalities in the gastric mucosa and were affected by both genetic- and sex-related factors. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12876-019-1009-x) contains supplementary material, which is available to authorized users. BioMed Central 2019-06-21 /pmc/articles/PMC6588904/ /pubmed/31226941 http://dx.doi.org/10.1186/s12876-019-1009-x Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Dantsuka, Ai Ichii, Osamu Hanberg, Annika Elewa, Yaser Hosny Ali Otsuka-Kanazawa, Saori Nakamura, Teppei Kon, Yasuhiro Histopathological features of the proper gastric glands in FVB/N-background mice carrying constitutively-active aryl-hydrocarbon receptor |
title | Histopathological features of the proper gastric glands in FVB/N-background mice carrying constitutively-active aryl-hydrocarbon receptor |
title_full | Histopathological features of the proper gastric glands in FVB/N-background mice carrying constitutively-active aryl-hydrocarbon receptor |
title_fullStr | Histopathological features of the proper gastric glands in FVB/N-background mice carrying constitutively-active aryl-hydrocarbon receptor |
title_full_unstemmed | Histopathological features of the proper gastric glands in FVB/N-background mice carrying constitutively-active aryl-hydrocarbon receptor |
title_short | Histopathological features of the proper gastric glands in FVB/N-background mice carrying constitutively-active aryl-hydrocarbon receptor |
title_sort | histopathological features of the proper gastric glands in fvb/n-background mice carrying constitutively-active aryl-hydrocarbon receptor |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6588904/ https://www.ncbi.nlm.nih.gov/pubmed/31226941 http://dx.doi.org/10.1186/s12876-019-1009-x |
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