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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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) |
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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 |
work_keys_str_mv |
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