Peroxisome Elevation Induces Stem Cell Differentiation and Intestinal Epithelial Repair.
Adolescent
Adult
Animals
Cell Differentiation
Colorectal Neoplasms
/ metabolism
Drosophila melanogaster
Female
Gene Expression Regulation
Humans
Inflammatory Bowel Diseases
/ metabolism
Intestinal Mucosa
/ cytology
Janus Kinases
/ genetics
Male
Mice
Mice, Inbred C57BL
Middle Aged
Peroxisomes
/ physiology
SOXB2 Transcription Factors
/ genetics
STAT Transcription Factors
/ genetics
Stem Cells
/ cytology
Young Adult
rab GTP-Binding Proteins
/ genetics
rab7 GTP-Binding Proteins
Drosophila
JAK and STAT signaling
SOX21A
differentiation
epithelial repair
inflammatory bowel disease
intestinal stem cells
late endosome maturation
peroxisome
Journal
Developmental cell
ISSN: 1878-1551
Titre abrégé: Dev Cell
Pays: United States
ID NLM: 101120028
Informations de publication
Date de publication:
20 04 2020
20 04 2020
Historique:
received:
06
11
2019
revised:
20
01
2020
accepted:
03
03
2020
pubmed:
4
4
2020
medline:
15
12
2020
entrez:
4
4
2020
Statut:
ppublish
Résumé
Epithelial-repair-dependent mucosal healing (MH) is associated with a more favorable prognosis for patients with inflammatory bowel disease (IBD). MH is accomplished via repair and regeneration of the intestinal epithelium. However, the mechanism underlying MH is ill defined. We found a striking upregulation of peroxisomes in the injured crypts of IBD patients. By increasing peroxisome levels in Drosophila midguts, we found that peroxisome elevation enhanced RAB7-dependent late endosome maturation, which then promoted stem and/or progenitor-cell differentiation via modulation of Janus Kinase (JAK) and Signal Transducer and Activator of Transcription (STAT)-SOX21A signaling. This in turn enhanced ISC-mediated regeneration. Importantly, RAB7 and SOX21 were upregulated in the crypts of IBD patients. Moreover, administration of drugs that increased peroxisome levels reversed the symptoms of dextran sulfate sodium (DSS)-induced colitis in mice. This study demonstrates a peroxisome-mediated epithelial repair mechanism, which opens a therapeutic avenue for the enhancement of MH in IBD patients.
Identifiants
pubmed: 32243783
pii: S1534-5807(20)30186-6
doi: 10.1016/j.devcel.2020.03.002
pii:
doi:
Substances chimiques
SOXB2 Transcription Factors
0
STAT Transcription Factors
0
rab7 GTP-Binding Proteins
0
rab7 GTP-binding proteins, human
0
rab7 GTP-binding proteins, mouse
0
Janus Kinases
EC 2.7.10.2
rab GTP-Binding Proteins
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
169-184.e11Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests The authors declare no competing interests.