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Peroxisome Elevation Induces Stem Cell Differentiation and Intestinal Epithelial Repair.
- Source :
-
Developmental cell [Dev Cell] 2020 Apr 20; Vol. 53 (2), pp. 169-184.e11. Date of Electronic Publication: 2020 Apr 02. - Publication Year :
- 2020
-
Abstract
- 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.<br />Competing Interests: Declaration of Interests The authors declare no competing interests.<br /> (Copyright © 2020 Elsevier Inc. All rights reserved.)
- Subjects :
- Adolescent
Adult
Animals
Colorectal Neoplasms metabolism
Drosophila melanogaster
Female
Humans
Inflammatory Bowel Diseases metabolism
Intestinal Mucosa injuries
Intestinal Mucosa metabolism
Janus Kinases genetics
Janus Kinases metabolism
Male
Mice
Mice, Inbred C57BL
Middle Aged
SOXB2 Transcription Factors genetics
SOXB2 Transcription Factors metabolism
STAT Transcription Factors genetics
STAT Transcription Factors metabolism
Young Adult
rab GTP-Binding Proteins genetics
rab GTP-Binding Proteins metabolism
rab7 GTP-Binding Proteins
Cell Differentiation
Colorectal Neoplasms pathology
Gene Expression Regulation
Inflammatory Bowel Diseases pathology
Intestinal Mucosa cytology
Peroxisomes physiology
Stem Cells cytology
Subjects
Details
- Language :
- English
- ISSN :
- 1878-1551
- Volume :
- 53
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Developmental cell
- Publication Type :
- Academic Journal
- Accession number :
- 32243783
- Full Text :
- https://doi.org/10.1016/j.devcel.2020.03.002