RRC ID 59186
Author Du G, Xiong L, Li X, Zhuo Z, Zhuang X, Yu Z, Wu L, Xiao D, Liu Z, Jie M, Liu X, Luo G, Guo Z, Chen H.
Title Peroxisome Elevation Induces Stem Cell Differentiation and Intestinal Epithelial Repair.
Journal Dev Cell
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.
Volume 53(2)
Pages 169-184.e11
Published 2020-4-20
DOI 10.1016/j.devcel.2020.03.002
PII S1534-5807(20)30186-6
PMID 32243783
MeSH Adolescent Adult Animals Cell Differentiation* Colorectal Neoplasms / metabolism Colorectal Neoplasms / pathology* Drosophila melanogaster Female Gene Expression Regulation* Humans Inflammatory Bowel Diseases / metabolism Inflammatory Bowel Diseases / pathology* Intestinal Mucosa / cytology* Intestinal Mucosa / injuries Intestinal Mucosa / metabolism Janus Kinases / genetics Janus Kinases / metabolism Male Mice Mice, Inbred C57BL Middle Aged Peroxisomes / physiology* SOXB2 Transcription Factors / genetics SOXB2 Transcription Factors / metabolism STAT Transcription Factors / genetics STAT Transcription Factors / metabolism Stem Cells / cytology* Young Adult rab GTP-Binding Proteins / genetics rab GTP-Binding Proteins / metabolism rab7 GTP-Binding Proteins
IF 10.092
Times Cited 0
Resource
Drosophila DGRC#109128