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

Autor: Takenori Kotani, Noriko Ihara, Saki Okamoto, Jajar Setiawan, Tasuku Konno, Yasuyuki Saito, Yoji Murata, Takashi Matozaki
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: PLoS ONE, Vol 16, Iss 8, p e0256774 (2021)
Druh dokumentu: article
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0256774
Popis: 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.
Databáze: Directory of Open Access Journals
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