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Conditional deletion of β1 integrins in the intestinal epithelium causes a loss of Hedgehog expression, intestinal hyperplasia, and early postnatal lethality

Conditional deletion of β1 integrins in the intestinal epithelium, unlike in epidermal and mammary epithelia, of mice does not result in decreased cell adhesion and proliferation, but instead causes a profound increase in epithelial proliferation with dysplasia and polypoid structures. The increased...

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Autores principales: Jones, Robert G., Li, Xiufen, Gray, Phillip D., Kuang, Jinqiu, Clayton, Frederic, Samowitz, Wade S., Madison, Blair B., Gumucio, Deborah L., Kuwada, Scott K.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2006
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064526/
https://www.ncbi.nlm.nih.gov/pubmed/17088430
http://dx.doi.org/10.1083/jcb.200602160
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author Jones, Robert G.
Li, Xiufen
Gray, Phillip D.
Kuang, Jinqiu
Clayton, Frederic
Samowitz, Wade S.
Madison, Blair B.
Gumucio, Deborah L.
Kuwada, Scott K.
author_facet Jones, Robert G.
Li, Xiufen
Gray, Phillip D.
Kuang, Jinqiu
Clayton, Frederic
Samowitz, Wade S.
Madison, Blair B.
Gumucio, Deborah L.
Kuwada, Scott K.
author_sort Jones, Robert G.
collection PubMed
description Conditional deletion of β1 integrins in the intestinal epithelium, unlike in epidermal and mammary epithelia, of mice does not result in decreased cell adhesion and proliferation, but instead causes a profound increase in epithelial proliferation with dysplasia and polypoid structures. The increased epithelial proliferation inhibited epithelial differentiation that caused severe malnutrition and early postnatal lethality. The striking similarities between β1 integrin–deleted mice and neonatal mice with defective Hedgehog signaling led to the discovery that Hedgehog expression was markedly reduced in the former mice. β1 integrins were found to drive the expression of Hedgehogs in intestinal epithelial cells in an HNF-3β (Foxa2)–dependent fashion. The expression of Tcf-4, a transcription factor known to be required for intestinal epithelial stem cell proliferation, was increased and mislocalized in the intestinal epithelia of the β1 integrin–deleted mice and in newborn mice treated with the Hedgehog signaling inhibitor cyclopamine. This study shows that β1 integrins are key regulators of proliferation and homeostasis in the intestine and achieve this not through anchorage-dependent effects but by generating Hh expression and signaling.
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spelling pubmed-20645262007-11-29 Conditional deletion of β1 integrins in the intestinal epithelium causes a loss of Hedgehog expression, intestinal hyperplasia, and early postnatal lethality Jones, Robert G. Li, Xiufen Gray, Phillip D. Kuang, Jinqiu Clayton, Frederic Samowitz, Wade S. Madison, Blair B. Gumucio, Deborah L. Kuwada, Scott K. J Cell Biol Research Articles Conditional deletion of β1 integrins in the intestinal epithelium, unlike in epidermal and mammary epithelia, of mice does not result in decreased cell adhesion and proliferation, but instead causes a profound increase in epithelial proliferation with dysplasia and polypoid structures. The increased epithelial proliferation inhibited epithelial differentiation that caused severe malnutrition and early postnatal lethality. The striking similarities between β1 integrin–deleted mice and neonatal mice with defective Hedgehog signaling led to the discovery that Hedgehog expression was markedly reduced in the former mice. β1 integrins were found to drive the expression of Hedgehogs in intestinal epithelial cells in an HNF-3β (Foxa2)–dependent fashion. The expression of Tcf-4, a transcription factor known to be required for intestinal epithelial stem cell proliferation, was increased and mislocalized in the intestinal epithelia of the β1 integrin–deleted mice and in newborn mice treated with the Hedgehog signaling inhibitor cyclopamine. This study shows that β1 integrins are key regulators of proliferation and homeostasis in the intestine and achieve this not through anchorage-dependent effects but by generating Hh expression and signaling. The Rockefeller University Press 2006-11-06 /pmc/articles/PMC2064526/ /pubmed/17088430 http://dx.doi.org/10.1083/jcb.200602160 Text en Copyright © 2006, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Research Articles
Jones, Robert G.
Li, Xiufen
Gray, Phillip D.
Kuang, Jinqiu
Clayton, Frederic
Samowitz, Wade S.
Madison, Blair B.
Gumucio, Deborah L.
Kuwada, Scott K.
Conditional deletion of β1 integrins in the intestinal epithelium causes a loss of Hedgehog expression, intestinal hyperplasia, and early postnatal lethality
title Conditional deletion of β1 integrins in the intestinal epithelium causes a loss of Hedgehog expression, intestinal hyperplasia, and early postnatal lethality
title_full Conditional deletion of β1 integrins in the intestinal epithelium causes a loss of Hedgehog expression, intestinal hyperplasia, and early postnatal lethality
title_fullStr Conditional deletion of β1 integrins in the intestinal epithelium causes a loss of Hedgehog expression, intestinal hyperplasia, and early postnatal lethality
title_full_unstemmed Conditional deletion of β1 integrins in the intestinal epithelium causes a loss of Hedgehog expression, intestinal hyperplasia, and early postnatal lethality
title_short Conditional deletion of β1 integrins in the intestinal epithelium causes a loss of Hedgehog expression, intestinal hyperplasia, and early postnatal lethality
title_sort conditional deletion of β1 integrins in the intestinal epithelium causes a loss of hedgehog expression, intestinal hyperplasia, and early postnatal lethality
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064526/
https://www.ncbi.nlm.nih.gov/pubmed/17088430
http://dx.doi.org/10.1083/jcb.200602160
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