1. Zebrafish modeling of intestinal injury, bacterial exposures and medications defines epithelial in vivo responses relevant to human inflammatory bowel disease.
- Author
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Chuang LS, Morrison J, Hsu NY, Labrias PR, Nayar S, Chen E, Villaverde N, Facey JA, Boschetti G, Giri M, Castillo-Martin M, Thin TH, Sharma Y, Chu J, and Cho JH
- Subjects
- Acids metabolism, Animals, Autophagy, Bacterial Proteins metabolism, Dextran Sulfate, Dinoprostone metabolism, Disease Models, Animal, Enterocytes metabolism, Humans, Inflammatory Bowel Diseases drug therapy, Intestines pathology, Lysosomes metabolism, Models, Biological, Mucins metabolism, Mucus metabolism, Epithelium pathology, Inflammatory Bowel Diseases microbiology, Inflammatory Bowel Diseases pathology, Intestines injuries, Zebrafish physiology
- 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.This article has an associated First Person interview with the first author of the paper., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2019. Published by The Company of Biologists Ltd.)
- Published
- 2019
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