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Active Transport of Bile Acids Decreases Mucin 2 in Neonatal Ileum: Implications for Development of Necrotizing Enterocolitis

Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency of premature infants, but its etiology remains unclear. We have previously shown that mucin 2 (Muc2) positive goblet cells are significantly decreased in NEC. We have also shown that ileal bile acids (BAs) are significantl...

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Autores principales: Martin, Nina A., Mount Patrick, Sarah K., Estrada, Teresa E., Frisk, Harrison A., Rogan, Daniel T., Dvorak, Bohuslav, Halpern, Melissa D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3230578/
https://www.ncbi.nlm.nih.gov/pubmed/22162748
http://dx.doi.org/10.1371/journal.pone.0027191
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author Martin, Nina A.
Mount Patrick, Sarah K.
Estrada, Teresa E.
Frisk, Harrison A.
Rogan, Daniel T.
Dvorak, Bohuslav
Halpern, Melissa D.
author_facet Martin, Nina A.
Mount Patrick, Sarah K.
Estrada, Teresa E.
Frisk, Harrison A.
Rogan, Daniel T.
Dvorak, Bohuslav
Halpern, Melissa D.
author_sort Martin, Nina A.
collection PubMed
description Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency of premature infants, but its etiology remains unclear. We have previously shown that mucin 2 (Muc2) positive goblet cells are significantly decreased in NEC. We have also shown that ileal bile acids (BAs) are significantly increased during the development of this disease. Because BAs can affect mucins, we hypothesized that elevated ileal BAs contribute to decreased Muc2 in experimental NEC. The role of Muc2 in NEC was evaluated in Winnie +/+ mice, a strain that produces aberrant Muc2. Muc2 and trefoil factor 3 (Tff3) were assessed in neonatal rats subjected to the NEC protocol when bile acids were removed, and in ileal explants from newborn and older rats cultured with and without BAs. Further, the role of active transport of BAs was determined using neonatal rats given the apical sodium dependent bile acid transporter (Asbt) inhibitor SC-435 and in neonatal Asbt knockout mice subjected to the NEC protocol. Mice with aberrant Muc2 had significantly greater incidence and severity of NEC. Using both in vivo and ex vivo techniques, we determined that BAs decrease Muc2 positive cells in neonatal but not older ileum. However, Tff3 positive cells are not decreased by BAs. In addition, active transport of BAs is required for BAs to decrease Muc2 in immature ileum. These data show that functional Muc2 plays a critical role in the prevention of NEC and BAs can potentiate the decreased Muc2 in disease development. Further, BAs have a more profound effect on Muc2 in immature versus older ileum, which may explain at least in part why NEC occurs almost exclusively in premature infants.
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spelling pubmed-32305782011-12-08 Active Transport of Bile Acids Decreases Mucin 2 in Neonatal Ileum: Implications for Development of Necrotizing Enterocolitis Martin, Nina A. Mount Patrick, Sarah K. Estrada, Teresa E. Frisk, Harrison A. Rogan, Daniel T. Dvorak, Bohuslav Halpern, Melissa D. PLoS One Research Article Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency of premature infants, but its etiology remains unclear. We have previously shown that mucin 2 (Muc2) positive goblet cells are significantly decreased in NEC. We have also shown that ileal bile acids (BAs) are significantly increased during the development of this disease. Because BAs can affect mucins, we hypothesized that elevated ileal BAs contribute to decreased Muc2 in experimental NEC. The role of Muc2 in NEC was evaluated in Winnie +/+ mice, a strain that produces aberrant Muc2. Muc2 and trefoil factor 3 (Tff3) were assessed in neonatal rats subjected to the NEC protocol when bile acids were removed, and in ileal explants from newborn and older rats cultured with and without BAs. Further, the role of active transport of BAs was determined using neonatal rats given the apical sodium dependent bile acid transporter (Asbt) inhibitor SC-435 and in neonatal Asbt knockout mice subjected to the NEC protocol. Mice with aberrant Muc2 had significantly greater incidence and severity of NEC. Using both in vivo and ex vivo techniques, we determined that BAs decrease Muc2 positive cells in neonatal but not older ileum. However, Tff3 positive cells are not decreased by BAs. In addition, active transport of BAs is required for BAs to decrease Muc2 in immature ileum. These data show that functional Muc2 plays a critical role in the prevention of NEC and BAs can potentiate the decreased Muc2 in disease development. Further, BAs have a more profound effect on Muc2 in immature versus older ileum, which may explain at least in part why NEC occurs almost exclusively in premature infants. Public Library of Science 2011-12-05 /pmc/articles/PMC3230578/ /pubmed/22162748 http://dx.doi.org/10.1371/journal.pone.0027191 Text en Martin et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Martin, Nina A.
Mount Patrick, Sarah K.
Estrada, Teresa E.
Frisk, Harrison A.
Rogan, Daniel T.
Dvorak, Bohuslav
Halpern, Melissa D.
Active Transport of Bile Acids Decreases Mucin 2 in Neonatal Ileum: Implications for Development of Necrotizing Enterocolitis
title Active Transport of Bile Acids Decreases Mucin 2 in Neonatal Ileum: Implications for Development of Necrotizing Enterocolitis
title_full Active Transport of Bile Acids Decreases Mucin 2 in Neonatal Ileum: Implications for Development of Necrotizing Enterocolitis
title_fullStr Active Transport of Bile Acids Decreases Mucin 2 in Neonatal Ileum: Implications for Development of Necrotizing Enterocolitis
title_full_unstemmed Active Transport of Bile Acids Decreases Mucin 2 in Neonatal Ileum: Implications for Development of Necrotizing Enterocolitis
title_short Active Transport of Bile Acids Decreases Mucin 2 in Neonatal Ileum: Implications for Development of Necrotizing Enterocolitis
title_sort active transport of bile acids decreases mucin 2 in neonatal ileum: implications for development of necrotizing enterocolitis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3230578/
https://www.ncbi.nlm.nih.gov/pubmed/22162748
http://dx.doi.org/10.1371/journal.pone.0027191
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