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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| creator | Kotani, Takenori Ihara, Noriko Okamoto, Saki Setiawan, Jajar Konno, Tasuku Saito, Yasuyuki Murata, Yoji Matozaki, Takashi |
| 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. |
| doi_str_mv | 10.1371/journal.pone.0256774 |
| format | Article |
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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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0256774</identifier><identifier>PMID: 34437645</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Ablation ; Analysis ; Animals ; Antibodies ; Biochemistry ; Biology and Life Sciences ; Carcinogenesis - genetics ; Cell proliferation ; Cell Proliferation - genetics ; Colon ; Colon - growth & development ; Colon - pathology ; Crosstalk ; Crypts ; Epidermal growth factor ; Epithelial cells ; Epithelium ; Ethylenediaminetetraacetic acid ; Gene expression ; Gene Expression Regulation, Neoplastic - genetics ; Goblet cells ; Goblet Cells - metabolism ; Homeostasis ; Homeostasis - genetics ; Humans ; Hyperplasia ; Intestinal Mucosa - growth & development ; Intestinal Mucosa - pathology ; Intestine ; Intestine, Small - metabolism ; K-Ras protein ; Kinases ; Ligands ; Medicine ; Medicine and Health Sciences ; Mice ; Molecular biology ; Mutation ; Organoids ; Organoids - metabolism ; Paneth cells ; Peptides ; Proto-Oncogene Proteins p21(ras) - genetics ; Regulation ; Research and Analysis Methods ; Signaling ; Small intestine ; Tumorigenesis ; University graduates ; Wnt protein ; Wnt Signaling Pathway - genetics</subject><ispartof>PloS one, 2021-08, Vol.16 (8), p.e0256774-e0256774</ispartof><rights>COPYRIGHT 2021 Public Library of Science</rights><rights>2021 Kotani et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>34437645</pmid><doi>10.1371/journal.pone.0256774</doi><tpages>e0256774</tpages><orcidid>https://orcid.org/0000-0002-4393-8416</orcidid><orcidid>https://orcid.org/0000-0001-8571-4210</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Ablation Analysis Animals Antibodies Biochemistry Biology and Life Sciences Carcinogenesis - genetics Cell proliferation Cell Proliferation - genetics Colon Colon - growth & development Colon - pathology Crosstalk Crypts Epidermal growth factor Epithelial cells Epithelium Ethylenediaminetetraacetic acid Gene expression Gene Expression Regulation, Neoplastic - genetics Goblet cells Goblet Cells - metabolism Homeostasis Homeostasis - genetics Humans Hyperplasia Intestinal Mucosa - growth & development Intestinal Mucosa - pathology Intestine Intestine, Small - metabolism K-Ras protein Kinases Ligands Medicine Medicine and Health Sciences Mice Molecular biology Mutation Organoids Organoids - metabolism Paneth cells Peptides Proto-Oncogene Proteins p21(ras) - genetics Regulation Research and Analysis Methods Signaling Small intestine Tumorigenesis University graduates Wnt protein Wnt Signaling Pathway - genetics |
| title | Role of Ras in regulation of intestinal epithelial cell homeostasis and crosstalk with Wnt signaling |
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