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

Ling shiang Chuang, Joshua Morrison, Nai yun Hsu, Philippe Ronel Labrias, Shikha Nayar, Ernie Chen, Nicole Villaverde, Jody Ann Facey, Gilles Boschetti, Mamta Giri, Mireia Castillo-Martin, Tin Htwe Thin, Yashoda Sharma, Jaime Chu, Judy H. Cho

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Genome-wide association studies have identified over 200 genomic loci associated with inflammatory bowel disease (IBD). High-effect risk alleles define key roles for genes involved in bacterial response and innate defense. 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. Prostaglandin E2 (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, whereas 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.

Original languageEnglish
Article numberdmm037432
JournalDMM Disease Models and Mechanisms
Volume12
Issue number8
DOIs
StatePublished - 2019

Keywords

  • Crohn's disease
  • DSS injury model
  • Epithelial barrier
  • IBD
  • Lysosome-rich enterocytes

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