Organoid-based epithelial to mesenchymal transition (OEMT) model: from an intestinal fibrosis perspective

Abstract The current in vitro or in vivo intestinal fibrosis models have many limitations. Recent advancements in the isolation and culturing of organoids has led to development of various three-dimensional (3D) intestinal disease models with in vivo physiology. In this study, we generated an organo...

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Autores principales:	Soojung Hahn, Myeong-Ok Nam, Jung Hyun Noh, Dong Hyeon Lee, Hyun Wook Han, Duk Hwan Kim, Ki Baik Hahm, Sung Pyo Hong, Jun-Hwan Yoo, Jongman Yoo
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ebee737219a842cf96b0be81c627d7ca
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spelling	oai:doaj.org-article:ebee737219a842cf96b0be81c627d7ca2021-12-02T12:30:17ZOrganoid-based epithelial to mesenchymal transition (OEMT) model: from an intestinal fibrosis perspective10.1038/s41598-017-02190-52045-2322https://doaj.org/article/ebee737219a842cf96b0be81c627d7ca2017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02190-5https://doaj.org/toc/2045-2322Abstract The current in vitro or in vivo intestinal fibrosis models have many limitations. Recent advancements in the isolation and culturing of organoids has led to development of various three-dimensional (3D) intestinal disease models with in vivo physiology. In this study, we generated an organoid-based epithelial to mesenchymal transition (OEMT) model, which could be used as a novel intestinal fibrosis model. Intestinal epithelial organoids (IEOs) were isolated and cultured from the small intestines of normal mice. IEOs were treated with transforming growth factor- β1 (TGF-β1) or Tumor necrosis factor-α (TNF-α) to evaluate their phenotypic change. Raw 264.7 cells (macrophage) stimulated with lipopolysaccharide were co-cultured with IEOs in growth media with or without TGF-β1. TGF-β1 alone slightly induced epithelial to mesenchymal transition (EMT) in the IEOs but mainly disrupted them. Macrophage released cytokines synergistically induced mesenchymal phenotypic changes in TGF-β1 stimulated intestinal organoids. TNF-α and TGF-β1 synergistically induced proliferation of mesenchymal cells as well as EMT in the IEOs. We generated a novel OEMT model based on our finding that TNF-α and TGF-β synergistically induce type 2 EMT in IEOs. This 3D EMT model with in vivo physiology could be used to study EMT associated intestinal fibrosis.Soojung HahnMyeong-Ok NamJung Hyun NohDong Hyeon LeeHyun Wook HanDuk Hwan KimKi Baik HahmSung Pyo HongJun-Hwan YooJongman YooNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Soojung Hahn Myeong-Ok Nam Jung Hyun Noh Dong Hyeon Lee Hyun Wook Han Duk Hwan Kim Ki Baik Hahm Sung Pyo Hong Jun-Hwan Yoo Jongman Yoo Organoid-based epithelial to mesenchymal transition (OEMT) model: from an intestinal fibrosis perspective
description	Abstract The current in vitro or in vivo intestinal fibrosis models have many limitations. Recent advancements in the isolation and culturing of organoids has led to development of various three-dimensional (3D) intestinal disease models with in vivo physiology. In this study, we generated an organoid-based epithelial to mesenchymal transition (OEMT) model, which could be used as a novel intestinal fibrosis model. Intestinal epithelial organoids (IEOs) were isolated and cultured from the small intestines of normal mice. IEOs were treated with transforming growth factor- β1 (TGF-β1) or Tumor necrosis factor-α (TNF-α) to evaluate their phenotypic change. Raw 264.7 cells (macrophage) stimulated with lipopolysaccharide were co-cultured with IEOs in growth media with or without TGF-β1. TGF-β1 alone slightly induced epithelial to mesenchymal transition (EMT) in the IEOs but mainly disrupted them. Macrophage released cytokines synergistically induced mesenchymal phenotypic changes in TGF-β1 stimulated intestinal organoids. TNF-α and TGF-β1 synergistically induced proliferation of mesenchymal cells as well as EMT in the IEOs. We generated a novel OEMT model based on our finding that TNF-α and TGF-β synergistically induce type 2 EMT in IEOs. This 3D EMT model with in vivo physiology could be used to study EMT associated intestinal fibrosis.
format	article
author	Soojung Hahn Myeong-Ok Nam Jung Hyun Noh Dong Hyeon Lee Hyun Wook Han Duk Hwan Kim Ki Baik Hahm Sung Pyo Hong Jun-Hwan Yoo Jongman Yoo
author_facet	Soojung Hahn Myeong-Ok Nam Jung Hyun Noh Dong Hyeon Lee Hyun Wook Han Duk Hwan Kim Ki Baik Hahm Sung Pyo Hong Jun-Hwan Yoo Jongman Yoo
author_sort	Soojung Hahn
title	Organoid-based epithelial to mesenchymal transition (OEMT) model: from an intestinal fibrosis perspective
title_short	Organoid-based epithelial to mesenchymal transition (OEMT) model: from an intestinal fibrosis perspective
title_full	Organoid-based epithelial to mesenchymal transition (OEMT) model: from an intestinal fibrosis perspective
title_fullStr	Organoid-based epithelial to mesenchymal transition (OEMT) model: from an intestinal fibrosis perspective
title_full_unstemmed	Organoid-based epithelial to mesenchymal transition (OEMT) model: from an intestinal fibrosis perspective
title_sort	organoid-based epithelial to mesenchymal transition (oemt) model: from an intestinal fibrosis perspective
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/ebee737219a842cf96b0be81c627d7ca
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_version_	1718394430868684800

Organoid-based epithelial to mesenchymal transition (OEMT) model: from an intestinal fibrosis perspective

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