PUBLICATION

Zebrafish modeling of intestinal injury, bacterial exposures, and medications defines epithelial in vivo responses relevant to human inflammatory bowel disease

Authors
Chuang, L.S., Morrison, J., Hsu, N.Y., Labrias, P.R., Nayar, S., Chen, E., Villaverde, N., Facey, J.A., Boschetti, G., Giri, M., Castillo-Martin, M., Thin, T.H., Sharma, Y., Chu, J., Cho, J.H.
ID
ZDB-PUB-190725-5
Date
2019
Source
Disease models & mechanisms   12(8): (Journal)
Registered Authors
Chuang, Ling-shiang (Felix), Chu, Jaime, Nayar, Shikha
Keywords
Crohn's disease, DSS injury model, Epithelial barrier, Inflammatory Bowel Disease, Lysosome-rich enterocytes, Zebrafish
MeSH Terms
  • Bacterial Proteins/metabolism
  • Epithelium/pathology*
  • Zebrafish/physiology*
  • Acids/metabolism
  • Disease Models, Animal
  • Dextran Sulfate
  • Lysosomes/metabolism
  • Intestines/injuries*
  • Intestines/pathology
  • Inflammatory Bowel Diseases/drug therapy
  • Inflammatory Bowel Diseases/microbiology*
  • Inflammatory Bowel Diseases/pathology*
  • Dinoprostone/metabolism
  • Models, Biological
  • Mucus/metabolism
  • Enterocytes/metabolism
  • Humans
  • Animals
  • Autophagy
  • Mucins/metabolism
(all 20)
PubMed
31337664 Full text @ Dis. Model. Mech.
Abstract
Genome-wide association studies have identified over 200 genomic loci associated to inflammatory bowel disease (IBD)1 High effect risk alleles define key roles for genes involved in bacterial response and innate defense2 More high-throughput in vivo systems are required to rapidly evaluate therapeutic agents. We visualize, in zebrafish, the effects on epithelial barrier function and intestinal autophagy of one-course and repetitive injury. Repetitive injury induces increased mortality, impaired recovery of intestinal barrier function, failure to contain bacteria within the intestine, and impaired autophagy. PGE2 administration protected against injury by enhancing epithelial barrier function and limiting systemic infection. Effects of IBD therapeutic agents were defined; mesalamine showed protective features during injury while 6-mercaptopurine displayed marked induction of autophagy during recovery. Given the highly conserved nature of innate defense in zebrafish, it represents an ideal model system with which to test established and new IBD therapies targeted to the epithelial barrier.
Genes / Markers
Figures
Figure Gallery (9 images)
Show all Figures
Expression
No data available
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
xt27TgTransgenic Insertion
    1 - 1 of 1
    Show
    Human Disease / Model
    No data available
    Sequence Targeting Reagents
    No data available
    Fish
    No data available
    Antibodies
    Name Type Antigen Genes Isotypes Host Organism
    Ab4-sqstm1polyclonalRabbit
    1 - 1 of 1
    Show
    Orthology
    No data available
    Engineered Foreign Genes
    Marker Marker Type Name
    mTurquoiseEFGmTurquoise
    1 - 1 of 1
    Show
    Mapping
    No data available
    Your Input Welcome
    We welcome your input and comments. Please use this form to recommend updates to the information in ZFIN. We appreciate as much detail as possible and references as appropriate. We will review your comments promptly.
    Citation
    Chuang, L.S., Morrison, J., Hsu, N.Y., Labrias, P.R., Nayar, S., Chen, E., Villaverde, N., Facey, J.A., Boschetti, G., Giri, M., Castillo-Martin, M., Thin, T.H., Sharma, Y., Chu, J., Cho, J.H. (2019) Zebrafish modeling of intestinal injury, bacterial exposures, and medications defines epithelial in vivo responses relevant to human inflammatory bowel disease. Disease models & mechanisms. 12(8):.