Regulation of colonic epithelial cell homeostasis by mTORC1

Abstract Cell signaling important for homeostatic regulation of colonic epithelial cells (CECs) remains poorly understood. Mammalian target of rapamycin complex 1 (mTORC1), a protein complex that contains the serine-threonine kinase mTOR, mediates signaling that underlies the control of cellular fun...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Takenori Kotani, Jajar Setiawan, Tasuku Konno, Noriko Ihara, Saki Okamoto, Yasuyuki Saito, Yoji Murata, Tetsuo Noda, Takashi Matozaki
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e259b404b0d9467a82163ad3fbd8cc8b
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:e259b404b0d9467a82163ad3fbd8cc8b
record_format	dspace
spelling	oai:doaj.org-article:e259b404b0d9467a82163ad3fbd8cc8b2021-12-02T18:50:55ZRegulation of colonic epithelial cell homeostasis by mTORC110.1038/s41598-020-70655-12045-2322https://doaj.org/article/e259b404b0d9467a82163ad3fbd8cc8b2020-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-70655-1https://doaj.org/toc/2045-2322Abstract Cell signaling important for homeostatic regulation of colonic epithelial cells (CECs) remains poorly understood. Mammalian target of rapamycin complex 1 (mTORC1), a protein complex that contains the serine-threonine kinase mTOR, mediates signaling that underlies the control of cellular functions such as proliferation and autophagy by various external stimuli. We here show that ablation of tuberous sclerosis complex 2 (Tsc2), a negative regulator of mTORC1, specifically in intestinal epithelial cells of mice resulted in increased activity of mTORC1 of, as well as increased proliferative activity of, CECs. Such Tsc2 ablation also reduced the population of Lgr5-positive colonic stem cells and the expression of Wnt target genes in CECs. The stimulatory phosphorylation of the kinase Akt and inhibitory phosphorylation of glycogen synthase kinase 3β were both markedly decreased in the colon of the Tsc2 conditional knockout (CKO) mice. Development of colonic organoids with cryptlike structures was enhanced for Tsc2 CKO mice compared with control mice. Finally, Tsc2 CKO mice manifested increased susceptibility to dextran sulfate sodium–induced colitis. Our results thus suggest that mTORC1 activity promotes the proliferation of, as well as the expression of Wnt target genes in, CECs and thereby contributes to colonic organogenesis and homeostasis.Takenori KotaniJajar SetiawanTasuku KonnoNoriko IharaSaki OkamotoYasuyuki SaitoYoji MurataTetsuo NodaTakashi MatozakiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-13 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Takenori Kotani Jajar Setiawan Tasuku Konno Noriko Ihara Saki Okamoto Yasuyuki Saito Yoji Murata Tetsuo Noda Takashi Matozaki Regulation of colonic epithelial cell homeostasis by mTORC1
description	Abstract Cell signaling important for homeostatic regulation of colonic epithelial cells (CECs) remains poorly understood. Mammalian target of rapamycin complex 1 (mTORC1), a protein complex that contains the serine-threonine kinase mTOR, mediates signaling that underlies the control of cellular functions such as proliferation and autophagy by various external stimuli. We here show that ablation of tuberous sclerosis complex 2 (Tsc2), a negative regulator of mTORC1, specifically in intestinal epithelial cells of mice resulted in increased activity of mTORC1 of, as well as increased proliferative activity of, CECs. Such Tsc2 ablation also reduced the population of Lgr5-positive colonic stem cells and the expression of Wnt target genes in CECs. The stimulatory phosphorylation of the kinase Akt and inhibitory phosphorylation of glycogen synthase kinase 3β were both markedly decreased in the colon of the Tsc2 conditional knockout (CKO) mice. Development of colonic organoids with cryptlike structures was enhanced for Tsc2 CKO mice compared with control mice. Finally, Tsc2 CKO mice manifested increased susceptibility to dextran sulfate sodium–induced colitis. Our results thus suggest that mTORC1 activity promotes the proliferation of, as well as the expression of Wnt target genes in, CECs and thereby contributes to colonic organogenesis and homeostasis.
format	article
author	Takenori Kotani Jajar Setiawan Tasuku Konno Noriko Ihara Saki Okamoto Yasuyuki Saito Yoji Murata Tetsuo Noda Takashi Matozaki
author_facet	Takenori Kotani Jajar Setiawan Tasuku Konno Noriko Ihara Saki Okamoto Yasuyuki Saito Yoji Murata Tetsuo Noda Takashi Matozaki
author_sort	Takenori Kotani
title	Regulation of colonic epithelial cell homeostasis by mTORC1
title_short	Regulation of colonic epithelial cell homeostasis by mTORC1
title_full	Regulation of colonic epithelial cell homeostasis by mTORC1
title_fullStr	Regulation of colonic epithelial cell homeostasis by mTORC1
title_full_unstemmed	Regulation of colonic epithelial cell homeostasis by mTORC1
title_sort	regulation of colonic epithelial cell homeostasis by mtorc1
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/e259b404b0d9467a82163ad3fbd8cc8b
work_keys_str_mv	AT takenorikotani regulationofcolonicepithelialcellhomeostasisbymtorc1 AT jajarsetiawan regulationofcolonicepithelialcellhomeostasisbymtorc1 AT tasukukonno regulationofcolonicepithelialcellhomeostasisbymtorc1 AT norikoihara regulationofcolonicepithelialcellhomeostasisbymtorc1 AT sakiokamoto regulationofcolonicepithelialcellhomeostasisbymtorc1 AT yasuyukisaito regulationofcolonicepithelialcellhomeostasisbymtorc1 AT yojimurata regulationofcolonicepithelialcellhomeostasisbymtorc1 AT tetsuonoda regulationofcolonicepithelialcellhomeostasisbymtorc1 AT takashimatozaki regulationofcolonicepithelialcellhomeostasisbymtorc1
_version_	1718377476122476544

Regulation of colonic epithelial cell homeostasis by mTORC1

Ejemplares similares