Role of Ras in regulation of intestinal epithelial cell homeostasis and crosstalk with Wnt signaling.
Animals
Carcinogenesis
/ genetics
Cell Proliferation
/ genetics
Colon
/ growth & development
Gene Expression Regulation, Neoplastic
/ genetics
Goblet Cells
/ metabolism
Homeostasis
/ genetics
Humans
Intestinal Mucosa
/ growth & development
Intestine, Small
/ metabolism
Mice
Organoids
/ metabolism
Proto-Oncogene Proteins p21(ras)
/ genetics
Wnt Signaling Pathway
/ genetics
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2021
2021
Historique:
received:
09
04
2021
accepted:
13
08
2021
entrez:
26
8
2021
pubmed:
27
8
2021
medline:
15
12
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 34437645
doi: 10.1371/journal.pone.0256774
pii: PONE-D-21-11849
pmc: PMC8389409
doi:
Substances chimiques
Hras protein, mouse
EC 3.6.5.2
Proto-Oncogene Proteins p21(ras)
EC 3.6.5.2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0256774Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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