Journal
DEVELOPMENTAL CELL
Volume 53, Issue 2, Pages 169-+Publisher
CELL PRESS
DOI: 10.1016/j.devcel.2020.03.002
Keywords
-
Categories
Funding
- National Key Research and Development Program Stem Cell and Translational Research Key Projects [2018YFA0108301]
- National Natural Science Foundation of China [31622031, 31671254, 91749110, 91753129]
- Guangdong Natural Science Funds for Distinguished Young Scholar [2016A030306037]
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available