Role of Ras in regulation of intestinal epithelial cell homeostasis and crosstalk with Wnt signaling.

Cross talk between different signaling pathways is thought to be important for regulation of homeostasis of, as well as oncogenesis of, the intestinal epithelium. Expression of an active form of K-Ras specifically in intestinal epithelial cells (IECs) of mice (IEC-RasDA mice) resulted in the develop...

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Autores principales: Takenori Kotani, Noriko Ihara, Saki Okamoto, Jajar Setiawan, Tasuku Konno, Yasuyuki Saito, Yoji Murata, Takashi Matozaki
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Publicado: Public Library of Science (PLoS) 2021
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spelling oai:doaj.org-article:3dc6677168d443738bc23e40aae51d3f2021-12-02T20:19:27ZRole of Ras in regulation of intestinal epithelial cell homeostasis and crosstalk with Wnt signaling.1932-620310.1371/journal.pone.0256774https://doaj.org/article/3dc6677168d443738bc23e40aae51d3f2021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0256774https://doaj.org/toc/1932-6203Cross talk between different signaling pathways is thought to be important for regulation of homeostasis of, as well as oncogenesis of, the intestinal epithelium. Expression of an active form of K-Ras specifically in intestinal epithelial cells (IECs) of mice (IEC-RasDA mice) resulted in the development of hyperplasia in the small intestine and colon of mice. IEC-RasDA mice also manifested the increased proliferation of IECs. In addition, the number of goblet cells markedly increased, while that of Paneth cells decreased in IEC-RasDA mice. Development of intestinal organoids was markedly enhanced for IEC-RasDA mice compared with control mice. Whereas, the expression of Wnt target genes was significantly reduced in the in intestinal crypts from IEC-RasDA mice compared with that apparent for the control. Our results thus suggest that K-Ras promotes the proliferation of IECs as well as generation of goblet cells. By contrast, Ras counter-regulates the Wnt signaling and thereby contribute to the proper regulation of intestinal epithelial cell homeostasis.Takenori KotaniNoriko IharaSaki OkamotoJajar SetiawanTasuku KonnoYasuyuki SaitoYoji MurataTakashi MatozakiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 8, p e0256774 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Takenori Kotani
Noriko Ihara
Saki Okamoto
Jajar Setiawan
Tasuku Konno
Yasuyuki Saito
Yoji Murata
Takashi Matozaki
Role of Ras in regulation of intestinal epithelial cell homeostasis and crosstalk with Wnt signaling.
description Cross talk between different signaling pathways is thought to be important for regulation of homeostasis of, as well as oncogenesis of, the intestinal epithelium. Expression of an active form of K-Ras specifically in intestinal epithelial cells (IECs) of mice (IEC-RasDA mice) resulted in the development of hyperplasia in the small intestine and colon of mice. IEC-RasDA mice also manifested the increased proliferation of IECs. In addition, the number of goblet cells markedly increased, while that of Paneth cells decreased in IEC-RasDA mice. Development of intestinal organoids was markedly enhanced for IEC-RasDA mice compared with control mice. Whereas, the expression of Wnt target genes was significantly reduced in the in intestinal crypts from IEC-RasDA mice compared with that apparent for the control. Our results thus suggest that K-Ras promotes the proliferation of IECs as well as generation of goblet cells. By contrast, Ras counter-regulates the Wnt signaling and thereby contribute to the proper regulation of intestinal epithelial cell homeostasis.
format article
author Takenori Kotani
Noriko Ihara
Saki Okamoto
Jajar Setiawan
Tasuku Konno
Yasuyuki Saito
Yoji Murata
Takashi Matozaki
author_facet Takenori Kotani
Noriko Ihara
Saki Okamoto
Jajar Setiawan
Tasuku Konno
Yasuyuki Saito
Yoji Murata
Takashi Matozaki
author_sort Takenori Kotani
title Role of Ras in regulation of intestinal epithelial cell homeostasis and crosstalk with Wnt signaling.
title_short Role of Ras in regulation of intestinal epithelial cell homeostasis and crosstalk with Wnt signaling.
title_full Role of Ras in regulation of intestinal epithelial cell homeostasis and crosstalk with Wnt signaling.
title_fullStr Role of Ras in regulation of intestinal epithelial cell homeostasis and crosstalk with Wnt signaling.
title_full_unstemmed Role of Ras in regulation of intestinal epithelial cell homeostasis and crosstalk with Wnt signaling.
title_sort role of ras in regulation of intestinal epithelial cell homeostasis and crosstalk with wnt signaling.
publisher Public Library of Science (PLoS)
publishDate 2021
url https://doaj.org/article/3dc6677168d443738bc23e40aae51d3f
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