MCL1 Is Required for Maintenance of Intestinal Homeostasis and Prevention of Carcinogenesis in Mice.
Animals
Apoptosis
/ genetics
Carcinogenesis
/ genetics
Carcinoma
/ diagnosis
Disease Models, Animal
Endoscopy
Epithelial Cells
/ pathology
Humans
Inflammatory Bowel Diseases
/ immunology
Intestinal Mucosa
/ diagnostic imaging
Intestinal Neoplasms
/ diagnosis
Mice
Mice, Transgenic
Myeloid Cell Leukemia Sequence 1 Protein
/ genetics
CRC
Cell Death
Colorectal Carcinoma
Tumorigenesis
Journal
Gastroenterology
ISSN: 1528-0012
Titre abrégé: Gastroenterology
Pays: United States
ID NLM: 0374630
Informations de publication
Date de publication:
07 2020
07 2020
Historique:
received:
21
03
2019
revised:
25
02
2020
accepted:
10
03
2020
pubmed:
18
3
2020
medline:
1
4
2021
entrez:
18
3
2020
Statut:
ppublish
Résumé
Intestinal epithelial homeostasis depends on a tightly regulated balance between intestinal epithelial cell (IEC) death and proliferation. While the disruption of several IEC death regulating factors result in intestinal inflammation, the loss of the anti-apoptotic BCL2 family members BCL2 and BCL2L1 has no effect on intestinal homeostasis in mice. We investigated the functions of the antiapoptotic protein MCL1, another member of the BCL2 family, in intestinal homeostasis in mice. We generated mice with IEC-specific disruption of Mcl1 (Mcl1 Mcl1 The antiapoptotic protein MCL1, a member of the BCL2 family, is required for maintenance of intestinal homeostasis and prevention of carcinogenesis in mice. Loss of MCL1 results in development of intestinal carcinomas, even under germ-free conditions, and therefore does not involve microbe-induced chronic inflammation. Mcl1
Sections du résumé
BACKGROUND & AIMS
Intestinal epithelial homeostasis depends on a tightly regulated balance between intestinal epithelial cell (IEC) death and proliferation. While the disruption of several IEC death regulating factors result in intestinal inflammation, the loss of the anti-apoptotic BCL2 family members BCL2 and BCL2L1 has no effect on intestinal homeostasis in mice. We investigated the functions of the antiapoptotic protein MCL1, another member of the BCL2 family, in intestinal homeostasis in mice.
METHODS
We generated mice with IEC-specific disruption of Mcl1 (Mcl1
RESULTS
Mcl1
CONCLUSION
The antiapoptotic protein MCL1, a member of the BCL2 family, is required for maintenance of intestinal homeostasis and prevention of carcinogenesis in mice. Loss of MCL1 results in development of intestinal carcinomas, even under germ-free conditions, and therefore does not involve microbe-induced chronic inflammation. Mcl1
Identifiants
pubmed: 32179094
pii: S0016-5085(20)30338-3
doi: 10.1053/j.gastro.2020.03.017
pmc: PMC7397524
pii:
doi:
Substances chimiques
Mcl1 protein, mouse
0
Myeloid Cell Leukemia Sequence 1 Protein
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
183-199Subventions
Organisme : Cancer Research UK
ID : A21139
Pays : United Kingdom
Organisme : Cancer Research UK
ID : A17196
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/J50032X/1
Pays : United Kingdom
Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.
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