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Intestinal Goblet Cell Loss during Chorioamnionitis in Fetal Lambs: Mechanistic Insights and Postnatal Implications

Chorioamnionitis, an important cause of preterm birth, is linked to necrotizing enterocolitis (NEC). NEC is characterized by a disrupted mucus barrier, goblet cell loss, and endoplasmic reticulum (ER) stress of the intestinal epithelium. These findings prompted us to investigate the mechanisms under...

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Autores principales: van Gorp, Charlotte, de Lange, Ilse H., Massy, Kimberly R. I., Kessels, Lilian, Jobe, Alan H., Cleutjens, Jack P. M., Kemp, Matthew W., Saito, Masatoshi, Usada, Haruo, Newnham, John, Hütten, Matthias, Kramer, Boris W., Zimmermann, Luc J., Wolfs, Tim G. A. M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920290/
https://www.ncbi.nlm.nih.gov/pubmed/33669331
http://dx.doi.org/10.3390/ijms22041946
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author van Gorp, Charlotte
de Lange, Ilse H.
Massy, Kimberly R. I.
Kessels, Lilian
Jobe, Alan H.
Cleutjens, Jack P. M.
Kemp, Matthew W.
Saito, Masatoshi
Usada, Haruo
Newnham, John
Hütten, Matthias
Kramer, Boris W.
Zimmermann, Luc J.
Wolfs, Tim G. A. M.
author_facet van Gorp, Charlotte
de Lange, Ilse H.
Massy, Kimberly R. I.
Kessels, Lilian
Jobe, Alan H.
Cleutjens, Jack P. M.
Kemp, Matthew W.
Saito, Masatoshi
Usada, Haruo
Newnham, John
Hütten, Matthias
Kramer, Boris W.
Zimmermann, Luc J.
Wolfs, Tim G. A. M.
author_sort van Gorp, Charlotte
collection PubMed
description Chorioamnionitis, an important cause of preterm birth, is linked to necrotizing enterocolitis (NEC). NEC is characterized by a disrupted mucus barrier, goblet cell loss, and endoplasmic reticulum (ER) stress of the intestinal epithelium. These findings prompted us to investigate the mechanisms underlying goblet cell alterations over time in an ovine chorioamnionitis model. Fetal lambs were intra-amniotically (IA) exposed to lipopolysaccharides (LPS) for 5, 12, or 24 h, or 2, 4, 8, or 15 d before premature delivery at 125 d gestational age (GA). Gut inflammation, the number, distribution, and differentiation of goblet cells, ER stress, and apoptosis were measured. We found a biphasic reduction in goblet cell numbers 24 h–2 d after, and 15 d after IA LPS exposure. The second decrease of goblet cell numbers was preceded by intestinal inflammation, apoptosis, and crypt ER stress, and increased SAM-pointed domain-containing ETS transcription factor (SPDEF)-positive cell counts. Our combined findings indicated that ER stress drives apoptosis of maturating goblet cells during chorioamnionitis, ultimately reducing goblet cell numbers. As similar changes have been described in patients suffering from NEC, these findings are considered to be clinically important for understanding the predecessors of NEC, and targeting ER stress in this context is interesting for future therapeutics.
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spelling pubmed-79202902021-03-02 Intestinal Goblet Cell Loss during Chorioamnionitis in Fetal Lambs: Mechanistic Insights and Postnatal Implications van Gorp, Charlotte de Lange, Ilse H. Massy, Kimberly R. I. Kessels, Lilian Jobe, Alan H. Cleutjens, Jack P. M. Kemp, Matthew W. Saito, Masatoshi Usada, Haruo Newnham, John Hütten, Matthias Kramer, Boris W. Zimmermann, Luc J. Wolfs, Tim G. A. M. Int J Mol Sci Article Chorioamnionitis, an important cause of preterm birth, is linked to necrotizing enterocolitis (NEC). NEC is characterized by a disrupted mucus barrier, goblet cell loss, and endoplasmic reticulum (ER) stress of the intestinal epithelium. These findings prompted us to investigate the mechanisms underlying goblet cell alterations over time in an ovine chorioamnionitis model. Fetal lambs were intra-amniotically (IA) exposed to lipopolysaccharides (LPS) for 5, 12, or 24 h, or 2, 4, 8, or 15 d before premature delivery at 125 d gestational age (GA). Gut inflammation, the number, distribution, and differentiation of goblet cells, ER stress, and apoptosis were measured. We found a biphasic reduction in goblet cell numbers 24 h–2 d after, and 15 d after IA LPS exposure. The second decrease of goblet cell numbers was preceded by intestinal inflammation, apoptosis, and crypt ER stress, and increased SAM-pointed domain-containing ETS transcription factor (SPDEF)-positive cell counts. Our combined findings indicated that ER stress drives apoptosis of maturating goblet cells during chorioamnionitis, ultimately reducing goblet cell numbers. As similar changes have been described in patients suffering from NEC, these findings are considered to be clinically important for understanding the predecessors of NEC, and targeting ER stress in this context is interesting for future therapeutics. MDPI 2021-02-16 /pmc/articles/PMC7920290/ /pubmed/33669331 http://dx.doi.org/10.3390/ijms22041946 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
van Gorp, Charlotte
de Lange, Ilse H.
Massy, Kimberly R. I.
Kessels, Lilian
Jobe, Alan H.
Cleutjens, Jack P. M.
Kemp, Matthew W.
Saito, Masatoshi
Usada, Haruo
Newnham, John
Hütten, Matthias
Kramer, Boris W.
Zimmermann, Luc J.
Wolfs, Tim G. A. M.
Intestinal Goblet Cell Loss during Chorioamnionitis in Fetal Lambs: Mechanistic Insights and Postnatal Implications
title Intestinal Goblet Cell Loss during Chorioamnionitis in Fetal Lambs: Mechanistic Insights and Postnatal Implications
title_full Intestinal Goblet Cell Loss during Chorioamnionitis in Fetal Lambs: Mechanistic Insights and Postnatal Implications
title_fullStr Intestinal Goblet Cell Loss during Chorioamnionitis in Fetal Lambs: Mechanistic Insights and Postnatal Implications
title_full_unstemmed Intestinal Goblet Cell Loss during Chorioamnionitis in Fetal Lambs: Mechanistic Insights and Postnatal Implications
title_short Intestinal Goblet Cell Loss during Chorioamnionitis in Fetal Lambs: Mechanistic Insights and Postnatal Implications
title_sort intestinal goblet cell loss during chorioamnionitis in fetal lambs: mechanistic insights and postnatal implications
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920290/
https://www.ncbi.nlm.nih.gov/pubmed/33669331
http://dx.doi.org/10.3390/ijms22041946
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