Chronic Inflammation in Ulcerative Colitis Causes Long-Term Changes in Goblet Cell FunctionSummary

Background & Aims: One of the features of ulcerative colitis (UC) is a defect in the protective mucus layer. This has been attributed to a reduced number of goblet cells (GCs). However, it is not known whether abnormal GC mucus secretion also contributes to the reduced mucus layer. Our aims...

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Autores principales:	Varsha Singh, Kelli Johnson, Jianyi Yin, Sun Lee, Ruxian Lin, Huimin Yu, Julie In, Jennifer Foulke-Abel, Nicholas C. Zachos, Mark Donowitz, Yan Rong
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2022
Materias:	Ulcerative Colitis Goblet Cell Mucus Layer Colonoids Diseases of the digestive system. Gastroenterology RC799-869
Acceso en línea:	https://doaj.org/article/25d5ffea77704c5ea3915cea053f586e
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spelling	oai:doaj.org-article:25d5ffea77704c5ea3915cea053f586e2021-11-14T04:34:13ZChronic Inflammation in Ulcerative Colitis Causes Long-Term Changes in Goblet Cell FunctionSummary2352-345X10.1016/j.jcmgh.2021.08.010https://doaj.org/article/25d5ffea77704c5ea3915cea053f586e2022-01-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2352345X21001776https://doaj.org/toc/2352-345XBackground & Aims: One of the features of ulcerative colitis (UC) is a defect in the protective mucus layer. This has been attributed to a reduced number of goblet cells (GCs). However, it is not known whether abnormal GC mucus secretion also contributes to the reduced mucus layer. Our aims were to investigate whether GC secretion was abnormal in UC and exists as a long-term effect of chronic inflammation. Methods: Colonoids were established from intestinal stem cells of healthy subjects (HS) and patients with UC. Colonoids were maintained as undifferentiated (UD) or induced to differentiate (DF) and studied as three-dimensional or monolayers on Transwell filters. Total RNA was extracted for quantitative real-time polymerase chain reaction analysis. Carbachol and prostaglandin E2 mediated mucin stimulation was examined by MUC2 IF/confocal microscopy and transmission electron microscopy. Results: Colonoids from UC patients can be propagated over many passages; however, they exhibit a reduced rate of growth and transepithelial electrical resistance compared with HS. Differentiated UC colonoid monolayers form a thin and non-continuous mucus layer. UC colonoids have increased expression of secretory lineage markers ATOH1 and SPDEF, along with MUC2 positive GCs, but failed to secrete mucin in response to the cholinergic agonist carbachol and prostaglandin E2, which caused increased secretion in HS. Exposure to tumor necrosis factor α (5 days) reduced the number of GCs, with a greater percentage decrease in UC colonoids compared with HS. Conclusions: Chronic inflammation in UC causes long-term changes in GCs, leading to abnormal mucus secretion. This continued defect in GC mucus secretion may contribute to the recurrence in UC.Varsha SinghKelli JohnsonJianyi YinSun LeeRuxian LinHuimin YuJulie InJennifer Foulke-AbelNicholas C. ZachosMark DonowitzYan RongElsevierarticleUlcerative ColitisGoblet CellMucus LayerColonoidsDiseases of the digestive system. GastroenterologyRC799-869ENCellular and Molecular Gastroenterology and Hepatology, Vol 13, Iss 1, Pp 219-232 (2022)
institution	DOAJ
collection	DOAJ
language	EN
topic	Ulcerative Colitis Goblet Cell Mucus Layer Colonoids Diseases of the digestive system. Gastroenterology RC799-869
spellingShingle	Ulcerative Colitis Goblet Cell Mucus Layer Colonoids Diseases of the digestive system. Gastroenterology RC799-869 Varsha Singh Kelli Johnson Jianyi Yin Sun Lee Ruxian Lin Huimin Yu Julie In Jennifer Foulke-Abel Nicholas C. Zachos Mark Donowitz Yan Rong Chronic Inflammation in Ulcerative Colitis Causes Long-Term Changes in Goblet Cell FunctionSummary
description	Background & Aims: One of the features of ulcerative colitis (UC) is a defect in the protective mucus layer. This has been attributed to a reduced number of goblet cells (GCs). However, it is not known whether abnormal GC mucus secretion also contributes to the reduced mucus layer. Our aims were to investigate whether GC secretion was abnormal in UC and exists as a long-term effect of chronic inflammation. Methods: Colonoids were established from intestinal stem cells of healthy subjects (HS) and patients with UC. Colonoids were maintained as undifferentiated (UD) or induced to differentiate (DF) and studied as three-dimensional or monolayers on Transwell filters. Total RNA was extracted for quantitative real-time polymerase chain reaction analysis. Carbachol and prostaglandin E2 mediated mucin stimulation was examined by MUC2 IF/confocal microscopy and transmission electron microscopy. Results: Colonoids from UC patients can be propagated over many passages; however, they exhibit a reduced rate of growth and transepithelial electrical resistance compared with HS. Differentiated UC colonoid monolayers form a thin and non-continuous mucus layer. UC colonoids have increased expression of secretory lineage markers ATOH1 and SPDEF, along with MUC2 positive GCs, but failed to secrete mucin in response to the cholinergic agonist carbachol and prostaglandin E2, which caused increased secretion in HS. Exposure to tumor necrosis factor α (5 days) reduced the number of GCs, with a greater percentage decrease in UC colonoids compared with HS. Conclusions: Chronic inflammation in UC causes long-term changes in GCs, leading to abnormal mucus secretion. This continued defect in GC mucus secretion may contribute to the recurrence in UC.
format	article
author	Varsha Singh Kelli Johnson Jianyi Yin Sun Lee Ruxian Lin Huimin Yu Julie In Jennifer Foulke-Abel Nicholas C. Zachos Mark Donowitz Yan Rong
author_facet	Varsha Singh Kelli Johnson Jianyi Yin Sun Lee Ruxian Lin Huimin Yu Julie In Jennifer Foulke-Abel Nicholas C. Zachos Mark Donowitz Yan Rong
author_sort	Varsha Singh
title	Chronic Inflammation in Ulcerative Colitis Causes Long-Term Changes in Goblet Cell FunctionSummary
title_short	Chronic Inflammation in Ulcerative Colitis Causes Long-Term Changes in Goblet Cell FunctionSummary
title_full	Chronic Inflammation in Ulcerative Colitis Causes Long-Term Changes in Goblet Cell FunctionSummary
title_fullStr	Chronic Inflammation in Ulcerative Colitis Causes Long-Term Changes in Goblet Cell FunctionSummary
title_full_unstemmed	Chronic Inflammation in Ulcerative Colitis Causes Long-Term Changes in Goblet Cell FunctionSummary
title_sort	chronic inflammation in ulcerative colitis causes long-term changes in goblet cell functionsummary
publisher	Elsevier
publishDate	2022
url	https://doaj.org/article/25d5ffea77704c5ea3915cea053f586e
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Chronic Inflammation in Ulcerative Colitis Causes Long-Term Changes in Goblet Cell FunctionSummary

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