ZFIN ID: ZDB-PUB-190725-5
Zebrafish modeling of intestinal injury, bacterial exposures, and medications defines epithelial in vivo responses relevant to human inflammatory bowel disease
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.
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:
  • Acids/metabolism
  • Animals
  • Autophagy
  • Bacterial Proteins/metabolism
  • Dextran Sulfate
  • Dinoprostone/metabolism
  • Disease Models, Animal
  • Enterocytes/metabolism
  • Epithelium/pathology*
  • Humans
  • Inflammatory Bowel Diseases/drug therapy
  • Inflammatory Bowel Diseases/microbiology*
  • Inflammatory Bowel Diseases/pathology*
  • Intestines/injuries*
  • Intestines/pathology
  • Lysosomes/metabolism
  • Models, Biological
  • Mucins/metabolism
  • Mucus/metabolism
  • Zebrafish/physiology*
PubMed: 31337664 Full text @ Dis. Model. Mech.
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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.
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