Cargando…
Antenatal Ureaplasma infection induces ovine small intestinal goblet cell defects: a strong link with NEC pathology
Disruption of the intestinal mucus barrier and intestinal epithelial endoplasmic reticulum (ER) stress contribute to necrotizing enterocolitis (NEC). Previously, we observed intestinal goblet cell loss and increased intestinal epithelial ER stress following chorioamnionitis. Here, we investigated ho...
Autores principales: | , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10606782/ https://www.ncbi.nlm.nih.gov/pubmed/36576242 http://dx.doi.org/10.1080/21688370.2022.2158016 |
_version_ | 1785127398438600704 |
---|---|
author | van Gorp, Charlotte de Lange, Ilse H Hütten, Matthias C López-Iglesias, Carmen Massy, Kimberly RI Kessels, Lilian Kramer, Boris van de Wetering, Willine Spiller, Brad Birchenough, George M van Gemert, Wim G Zimmermann, Luc J Wolfs, Tim GAM |
author_facet | van Gorp, Charlotte de Lange, Ilse H Hütten, Matthias C López-Iglesias, Carmen Massy, Kimberly RI Kessels, Lilian Kramer, Boris van de Wetering, Willine Spiller, Brad Birchenough, George M van Gemert, Wim G Zimmermann, Luc J Wolfs, Tim GAM |
author_sort | van Gorp, Charlotte |
collection | PubMed |
description | Disruption of the intestinal mucus barrier and intestinal epithelial endoplasmic reticulum (ER) stress contribute to necrotizing enterocolitis (NEC). Previously, we observed intestinal goblet cell loss and increased intestinal epithelial ER stress following chorioamnionitis. Here, we investigated how chorioamnionitis affects goblet cells by assessing their cellular characteristics. Importantly, goblet cell features are compared with those in clinical NEC biopsies. Mucus thickness was assessed as read-out of goblet cell function. Fetal lambs were intra-amniotically (IA) infected for 7d at 122 gestational age with Ureaplasma parvum serovar-3, the main microorganism clinically associated with chorioamnionitis. After preterm delivery, mucus thickness, goblet cell numbers, gut inflammation, epithelial proliferation and apoptosis and intestinal epithelial ER stress were investigated in the terminal ileum. Next, goblet cell morphological alterations (TEM) were studied and compared to human NEC samples. Ileal mucus thickness and goblet cell numbers were elevated following IA UP exposure. Increased pro-apoptotic ER stress, detected by elevated CHOP-positive cell counts and disrupted organelle morphology of secretory cells in the intestinal epithelium, was observed in IA UP exposed animals. Importantly, comparable cellular morphological alterations were observed in the ileum from NEC patients. In conclusion, UP-driven chorioamnionitis leads to a thickened ileal mucus layer and mucus hypersecretion from goblet cells. Since this was associated with pro-apoptotic ER stress and organelle disruption, mucus barrier alterations seem to occur at the expense of goblet cell resilience and may therefore predispose to detrimental intestinal outcomes. The remarkable overlap of these in utero findings with observations in NEC patients underscores their clinical relevance. |
format | Online Article Text |
id | pubmed-10606782 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-106067822023-10-28 Antenatal Ureaplasma infection induces ovine small intestinal goblet cell defects: a strong link with NEC pathology van Gorp, Charlotte de Lange, Ilse H Hütten, Matthias C López-Iglesias, Carmen Massy, Kimberly RI Kessels, Lilian Kramer, Boris van de Wetering, Willine Spiller, Brad Birchenough, George M van Gemert, Wim G Zimmermann, Luc J Wolfs, Tim GAM Tissue Barriers Research Article Disruption of the intestinal mucus barrier and intestinal epithelial endoplasmic reticulum (ER) stress contribute to necrotizing enterocolitis (NEC). Previously, we observed intestinal goblet cell loss and increased intestinal epithelial ER stress following chorioamnionitis. Here, we investigated how chorioamnionitis affects goblet cells by assessing their cellular characteristics. Importantly, goblet cell features are compared with those in clinical NEC biopsies. Mucus thickness was assessed as read-out of goblet cell function. Fetal lambs were intra-amniotically (IA) infected for 7d at 122 gestational age with Ureaplasma parvum serovar-3, the main microorganism clinically associated with chorioamnionitis. After preterm delivery, mucus thickness, goblet cell numbers, gut inflammation, epithelial proliferation and apoptosis and intestinal epithelial ER stress were investigated in the terminal ileum. Next, goblet cell morphological alterations (TEM) were studied and compared to human NEC samples. Ileal mucus thickness and goblet cell numbers were elevated following IA UP exposure. Increased pro-apoptotic ER stress, detected by elevated CHOP-positive cell counts and disrupted organelle morphology of secretory cells in the intestinal epithelium, was observed in IA UP exposed animals. Importantly, comparable cellular morphological alterations were observed in the ileum from NEC patients. In conclusion, UP-driven chorioamnionitis leads to a thickened ileal mucus layer and mucus hypersecretion from goblet cells. Since this was associated with pro-apoptotic ER stress and organelle disruption, mucus barrier alterations seem to occur at the expense of goblet cell resilience and may therefore predispose to detrimental intestinal outcomes. The remarkable overlap of these in utero findings with observations in NEC patients underscores their clinical relevance. Taylor & Francis 2022-12-28 /pmc/articles/PMC10606782/ /pubmed/36576242 http://dx.doi.org/10.1080/21688370.2022.2158016 Text en © 2022 The Author(s). Published with license by Taylor & Francis Group, LLC. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) ), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way. The terms on which this article has been published allow the posting of the Accepted Manuscript in a repository by the author(s) or with their consent. |
spellingShingle | Research Article van Gorp, Charlotte de Lange, Ilse H Hütten, Matthias C López-Iglesias, Carmen Massy, Kimberly RI Kessels, Lilian Kramer, Boris van de Wetering, Willine Spiller, Brad Birchenough, George M van Gemert, Wim G Zimmermann, Luc J Wolfs, Tim GAM Antenatal Ureaplasma infection induces ovine small intestinal goblet cell defects: a strong link with NEC pathology |
title | Antenatal Ureaplasma infection induces ovine small intestinal goblet cell defects: a strong link with NEC pathology |
title_full | Antenatal Ureaplasma infection induces ovine small intestinal goblet cell defects: a strong link with NEC pathology |
title_fullStr | Antenatal Ureaplasma infection induces ovine small intestinal goblet cell defects: a strong link with NEC pathology |
title_full_unstemmed | Antenatal Ureaplasma infection induces ovine small intestinal goblet cell defects: a strong link with NEC pathology |
title_short | Antenatal Ureaplasma infection induces ovine small intestinal goblet cell defects: a strong link with NEC pathology |
title_sort | antenatal ureaplasma infection induces ovine small intestinal goblet cell defects: a strong link with nec pathology |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10606782/ https://www.ncbi.nlm.nih.gov/pubmed/36576242 http://dx.doi.org/10.1080/21688370.2022.2158016 |
work_keys_str_mv | AT vangorpcharlotte antenatalureaplasmainfectioninducesovinesmallintestinalgobletcelldefectsastronglinkwithnecpathology AT delangeilseh antenatalureaplasmainfectioninducesovinesmallintestinalgobletcelldefectsastronglinkwithnecpathology AT huttenmatthiasc antenatalureaplasmainfectioninducesovinesmallintestinalgobletcelldefectsastronglinkwithnecpathology AT lopeziglesiascarmen antenatalureaplasmainfectioninducesovinesmallintestinalgobletcelldefectsastronglinkwithnecpathology AT massykimberlyri antenatalureaplasmainfectioninducesovinesmallintestinalgobletcelldefectsastronglinkwithnecpathology AT kesselslilian antenatalureaplasmainfectioninducesovinesmallintestinalgobletcelldefectsastronglinkwithnecpathology AT kramerboris antenatalureaplasmainfectioninducesovinesmallintestinalgobletcelldefectsastronglinkwithnecpathology AT vandeweteringwilline antenatalureaplasmainfectioninducesovinesmallintestinalgobletcelldefectsastronglinkwithnecpathology AT spillerbrad antenatalureaplasmainfectioninducesovinesmallintestinalgobletcelldefectsastronglinkwithnecpathology AT birchenoughgeorgem antenatalureaplasmainfectioninducesovinesmallintestinalgobletcelldefectsastronglinkwithnecpathology AT vangemertwimg antenatalureaplasmainfectioninducesovinesmallintestinalgobletcelldefectsastronglinkwithnecpathology AT zimmermannlucj antenatalureaplasmainfectioninducesovinesmallintestinalgobletcelldefectsastronglinkwithnecpathology AT wolfstimgam antenatalureaplasmainfectioninducesovinesmallintestinalgobletcelldefectsastronglinkwithnecpathology |