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RNA-binding protein HuR promotes growth of small intestinal mucosa by activating the Wnt signaling pathway

Inhibition of growth of the intestinal epithelium, a rapidly self-renewing tissue, is commonly found in various critical disorders. The RNA-binding protein HuR is highly expressed in the gut mucosa and modulates the stability and translation of target mRNAs, but its exact biological function in the...

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Autores principales: Liu, Lan, Christodoulou-Vafeiadou, Eleni, Rao, Jaladanki N., Zou, Tongtong, Xiao, Lan, Kyoung Chung, Hee, Yang, Hong, Gorospe, Myriam, Kontoyiannis, Dimitris, Wang, Jian-Ying
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4214778/
https://www.ncbi.nlm.nih.gov/pubmed/25165135
http://dx.doi.org/10.1091/mbc.E14-03-0853
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author Liu, Lan
Christodoulou-Vafeiadou, Eleni
Rao, Jaladanki N.
Zou, Tongtong
Xiao, Lan
Kyoung Chung, Hee
Yang, Hong
Gorospe, Myriam
Kontoyiannis, Dimitris
Wang, Jian-Ying
author_facet Liu, Lan
Christodoulou-Vafeiadou, Eleni
Rao, Jaladanki N.
Zou, Tongtong
Xiao, Lan
Kyoung Chung, Hee
Yang, Hong
Gorospe, Myriam
Kontoyiannis, Dimitris
Wang, Jian-Ying
author_sort Liu, Lan
collection PubMed
description Inhibition of growth of the intestinal epithelium, a rapidly self-renewing tissue, is commonly found in various critical disorders. The RNA-binding protein HuR is highly expressed in the gut mucosa and modulates the stability and translation of target mRNAs, but its exact biological function in the intestinal epithelium remains unclear. Here, we investigated the role of HuR in intestinal homeostasis using a genetic model and further defined its target mRNAs. Targeted deletion of HuR in intestinal epithelial cells caused significant mucosal atrophy in the small intestine, as indicated by decreased cell proliferation within the crypts and subsequent shrinkages of crypts and villi. In addition, the HuR-deficient intestinal epithelium also displayed decreased regenerative potential of crypt progenitors after exposure to irradiation. HuR deficiency decreased expression of the Wnt coreceptor LDL receptor–related protein 6 (LRP6) in the mucosal tissues. At the molecular level, HuR was found to bind the Lrp6 mRNA via its 3′-untranslated region and enhanced LRP6 expression by stabilizing Lrp6 mRNA and stimulating its translation. These results indicate that HuR is essential for normal mucosal growth in the small intestine by altering Wnt signals through up-regulation of LRP6 expression and highlight a novel role of HuR deficiency in the pathogenesis of intestinal mucosal atrophy under pathological conditions.
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spelling pubmed-42147782015-01-16 RNA-binding protein HuR promotes growth of small intestinal mucosa by activating the Wnt signaling pathway Liu, Lan Christodoulou-Vafeiadou, Eleni Rao, Jaladanki N. Zou, Tongtong Xiao, Lan Kyoung Chung, Hee Yang, Hong Gorospe, Myriam Kontoyiannis, Dimitris Wang, Jian-Ying Mol Biol Cell Articles Inhibition of growth of the intestinal epithelium, a rapidly self-renewing tissue, is commonly found in various critical disorders. The RNA-binding protein HuR is highly expressed in the gut mucosa and modulates the stability and translation of target mRNAs, but its exact biological function in the intestinal epithelium remains unclear. Here, we investigated the role of HuR in intestinal homeostasis using a genetic model and further defined its target mRNAs. Targeted deletion of HuR in intestinal epithelial cells caused significant mucosal atrophy in the small intestine, as indicated by decreased cell proliferation within the crypts and subsequent shrinkages of crypts and villi. In addition, the HuR-deficient intestinal epithelium also displayed decreased regenerative potential of crypt progenitors after exposure to irradiation. HuR deficiency decreased expression of the Wnt coreceptor LDL receptor–related protein 6 (LRP6) in the mucosal tissues. At the molecular level, HuR was found to bind the Lrp6 mRNA via its 3′-untranslated region and enhanced LRP6 expression by stabilizing Lrp6 mRNA and stimulating its translation. These results indicate that HuR is essential for normal mucosal growth in the small intestine by altering Wnt signals through up-regulation of LRP6 expression and highlight a novel role of HuR deficiency in the pathogenesis of intestinal mucosal atrophy under pathological conditions. The American Society for Cell Biology 2014-11-01 /pmc/articles/PMC4214778/ /pubmed/25165135 http://dx.doi.org/10.1091/mbc.E14-03-0853 Text en © 2014 Liu, Christodoulou-Vafeiadou, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons
.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology.
spellingShingle Articles
Liu, Lan
Christodoulou-Vafeiadou, Eleni
Rao, Jaladanki N.
Zou, Tongtong
Xiao, Lan
Kyoung Chung, Hee
Yang, Hong
Gorospe, Myriam
Kontoyiannis, Dimitris
Wang, Jian-Ying
RNA-binding protein HuR promotes growth of small intestinal mucosa by activating the Wnt signaling pathway
title RNA-binding protein HuR promotes growth of small intestinal mucosa by activating the Wnt signaling pathway
title_full RNA-binding protein HuR promotes growth of small intestinal mucosa by activating the Wnt signaling pathway
title_fullStr RNA-binding protein HuR promotes growth of small intestinal mucosa by activating the Wnt signaling pathway
title_full_unstemmed RNA-binding protein HuR promotes growth of small intestinal mucosa by activating the Wnt signaling pathway
title_short RNA-binding protein HuR promotes growth of small intestinal mucosa by activating the Wnt signaling pathway
title_sort rna-binding protein hur promotes growth of small intestinal mucosa by activating the wnt signaling pathway
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4214778/
https://www.ncbi.nlm.nih.gov/pubmed/25165135
http://dx.doi.org/10.1091/mbc.E14-03-0853
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