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A Novel Role of Spred2 in the Colonic Epithelial Cell Homeostasis and Inflammation

Rapid and adequate mucosal healing is important for a remission of ulcerative colitis (UC) patients. Here, we examined whether Spred2, a member of the Sprouty-related EVH1-domain-containing proteins that inhibit the Ras/Raf/ERK pathway, plays a role in colonic mucosal homeostasis and inflammation by...

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Autores principales: Takahashi, Sakuma, Yoshimura, Teizo, Ohkura, Takahiro, Fujisawa, Masayoshi, Fushimi, Soichiro, Ito, Toshihiro, Itakura, Junya, Hiraoka, Sakiko, Okada, Hiroyuki, Yamamoto, Kazuhide, Matsukawa, Akihiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5116627/
https://www.ncbi.nlm.nih.gov/pubmed/27869219
http://dx.doi.org/10.1038/srep37531
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author Takahashi, Sakuma
Yoshimura, Teizo
Ohkura, Takahiro
Fujisawa, Masayoshi
Fushimi, Soichiro
Ito, Toshihiro
Itakura, Junya
Hiraoka, Sakiko
Okada, Hiroyuki
Yamamoto, Kazuhide
Matsukawa, Akihiro
author_facet Takahashi, Sakuma
Yoshimura, Teizo
Ohkura, Takahiro
Fujisawa, Masayoshi
Fushimi, Soichiro
Ito, Toshihiro
Itakura, Junya
Hiraoka, Sakiko
Okada, Hiroyuki
Yamamoto, Kazuhide
Matsukawa, Akihiro
author_sort Takahashi, Sakuma
collection PubMed
description Rapid and adequate mucosal healing is important for a remission of ulcerative colitis (UC) patients. Here, we examined whether Spred2, a member of the Sprouty-related EVH1-domain-containing proteins that inhibit the Ras/Raf/ERK pathway, plays a role in colonic mucosal homeostasis and inflammation by using Spred2 knockout (KO) mice. We first detected increased epithelial cell proliferation and cadherin 1 expression in the colon of naïve Spred2 KO mice compared to wild-type mice. Interestingly, Spred2 KO mice were resistant to dextran sulfate sodium (DSS)-induced acute colitis as indicated by lower levels of body weight loss and disease activity index. Histologically, epithelial cell injury and inflammation were milder in the colonic mucosa of Spred2 KO mice on day 3 and almost undetectable by day 8. Experiments with bone chimeric mice indicated that Spred2-deficiency in non-hematopoietic cells was responsible for the reduced sensitivity to DSS. Finally, Spred2 KO mice developed significantly fewer tumors in response to azoxymethane plus DSS. Taken together, our results demonstrate, for the first time, that Spred2 plays an important role in the regulation of colonic epithelial cell proliferation and inflammation by potentially down-regulating the activation of ERK. Thus, Spred2 may be a new therapeutic target for the treatment of UC.
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spelling pubmed-51166272016-11-28 A Novel Role of Spred2 in the Colonic Epithelial Cell Homeostasis and Inflammation Takahashi, Sakuma Yoshimura, Teizo Ohkura, Takahiro Fujisawa, Masayoshi Fushimi, Soichiro Ito, Toshihiro Itakura, Junya Hiraoka, Sakiko Okada, Hiroyuki Yamamoto, Kazuhide Matsukawa, Akihiro Sci Rep Article Rapid and adequate mucosal healing is important for a remission of ulcerative colitis (UC) patients. Here, we examined whether Spred2, a member of the Sprouty-related EVH1-domain-containing proteins that inhibit the Ras/Raf/ERK pathway, plays a role in colonic mucosal homeostasis and inflammation by using Spred2 knockout (KO) mice. We first detected increased epithelial cell proliferation and cadherin 1 expression in the colon of naïve Spred2 KO mice compared to wild-type mice. Interestingly, Spred2 KO mice were resistant to dextran sulfate sodium (DSS)-induced acute colitis as indicated by lower levels of body weight loss and disease activity index. Histologically, epithelial cell injury and inflammation were milder in the colonic mucosa of Spred2 KO mice on day 3 and almost undetectable by day 8. Experiments with bone chimeric mice indicated that Spred2-deficiency in non-hematopoietic cells was responsible for the reduced sensitivity to DSS. Finally, Spred2 KO mice developed significantly fewer tumors in response to azoxymethane plus DSS. Taken together, our results demonstrate, for the first time, that Spred2 plays an important role in the regulation of colonic epithelial cell proliferation and inflammation by potentially down-regulating the activation of ERK. Thus, Spred2 may be a new therapeutic target for the treatment of UC. Nature Publishing Group 2016-11-21 /pmc/articles/PMC5116627/ /pubmed/27869219 http://dx.doi.org/10.1038/srep37531 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Takahashi, Sakuma
Yoshimura, Teizo
Ohkura, Takahiro
Fujisawa, Masayoshi
Fushimi, Soichiro
Ito, Toshihiro
Itakura, Junya
Hiraoka, Sakiko
Okada, Hiroyuki
Yamamoto, Kazuhide
Matsukawa, Akihiro
A Novel Role of Spred2 in the Colonic Epithelial Cell Homeostasis and Inflammation
title A Novel Role of Spred2 in the Colonic Epithelial Cell Homeostasis and Inflammation
title_full A Novel Role of Spred2 in the Colonic Epithelial Cell Homeostasis and Inflammation
title_fullStr A Novel Role of Spred2 in the Colonic Epithelial Cell Homeostasis and Inflammation
title_full_unstemmed A Novel Role of Spred2 in the Colonic Epithelial Cell Homeostasis and Inflammation
title_short A Novel Role of Spred2 in the Colonic Epithelial Cell Homeostasis and Inflammation
title_sort novel role of spred2 in the colonic epithelial cell homeostasis and inflammation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5116627/
https://www.ncbi.nlm.nih.gov/pubmed/27869219
http://dx.doi.org/10.1038/srep37531
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