ArticleDevelopmental biology2016
Ibuprofen slows migration and inhibits bowel colonization by enteric nervous system precursors in zebrafish, chick and mouse.
Article in Developmental biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 49 citations in OpenAlex.
- Sporadic Hirschsprung Disease: Mutational Spectrum and Novel Candidate Genes Revealed by Next-generation Sequencing.Scientific reports · 2017Trial
- NSAID-mediated cyclooxygenase inhibition disrupts ectodermal derivative formation in axolotl embryos.bioRxiv : the preprint server for biology · 2025Article
- Spatiotemporal characterization of cyclooxygenase pathway enzymes during vertebrate embryonic development.Developmental biology · 2025Article
- The Oxidative Stress and Nervous Distress Connection in Gastrointestinal Disorders.Biomolecules · 2023Review
- Suppression of PGE2/EP2 signaling alleviates Hirschsprung disease by upregulating p38 mitogen-activated protein kinase activity.Journal of molecular medicine (Berlin, Germany) · 2023Article
- Nonsteroidal anti-inflammatory drugs and implications for the cyclooxygenase pathway in embryonic development.American journal of physiology. Cell physiology · 2023Review
- Time to go: neural crest cell epithelial-to-mesenchymal transition.Development (Cambridge, England) · 2022Review
- Recent advances in understanding the roles of the enteric nervous system.Faculty reviews · 2022Review
- Ibuprofen does not inhibit RhoA-mediated growth cone collapse of embryonic chicken retinal axons by LPA.Experimental brain research · 2021Article
- Dynamic integration of enteric neural stem cells in ex vivo organotypic colon cultures.Scientific reports · 2021Article
- Disorders of the enteric nervous system - a holistic view.Nature reviews. Gastroenterology & hepatology · 2021Review
- Zebrafish: A Model Organism for Studying Enteric Nervous System Development and Disease.Frontiers in cell and developmental biology · 2020Review
- Gut microbiota-mediated Gene-Environment interaction in the TashT mouse model of Hirschsprung disease.Scientific reports · 2019Article
- Advances in Enteric Neurobiology: The "Brain" in the Gut in Health and Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Review
- Muscularis macrophage development in the absence of an enteric nervous system.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Hirschsprung disease - integrating basic science and clinical medicine to improve outcomes.Nature reviews. Gastroenterology & hepatology · 2018Review
- Hirschsprung's disease: clinical dysmorphology, genes, micro-RNAs, and future perspectives.Pediatric research · 2017Review
- Gene-environment interactions in development and disease.Wiley interdisciplinary reviews. Developmental biology · 2017Review
- A Novel Zebrafish ret Heterozygous Model of Hirschsprung Disease Identifies a Functional Role for mapk10 as a Modifier of Enteric Nervous System Phenotype Severity.PLoS genetics · 2016Article
- White paper on guidelines concerning enteric nervous system stem cell therapy for enteric neuropathies.Developmental biology · 2016Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
Hirschsprung Disease (HSCR) is a potentially deadly birth defect characterized by the absence of the enteric nervous system (ENS) in distal bowel. Although HSCR has clear genetic causes, no HSCR-associated mutation is 100% penetrant, suggesting gene-gene and gene-environment interactions determine HSCR occurrence. To test the hypothesis that certain medicines might alter HSCR risk we treated zebrafish with medications commonly used during early human pregnancy and discovered that ibuprofen caused HSCR-like absence of enteric neurons in distal bowel. Using fetal CF-1 mouse gut slice cultures, we found that ibuprofen treated enteric neural crest-derived cells (ENCDC) had reduced migration, fewer lamellipodia and lower levels of active RAC1/CDC42. Additionally, inhibiting ROCK, a RHOA effector and known RAC1 antagonist, reversed ibuprofen effects on migrating mouse ENCDC in culture. Ibuprofen also inhibited colonization of Ret+/- mouse bowel by ENCDC in vivo and dramatically reduced bowel colonization by chick ENCDC in culture. Interestingly, ibuprofen did not affect ENCDC migration until after at least three hours of exposure. Furthermore, mice deficient in Ptgs1 (COX 1) and Ptgs2 (COX 2) had normal bowel colonization by ENCDC and normal ENCDC migration in vitro suggesting COX-independent effects. Consistent with selective and strain specific effects on ENCDC, ibuprofen did not affect migration of gut mesenchymal cells, NIH3T3, or WT C57BL/6 ENCDC, and did not affect dorsal root ganglion cell precursor migration in zebrafish. Thus, ibuprofen inhibits ENCDC migration in vitro and bowel colonization by ENCDC in vivo in zebrafish, mouse and chick, but there are cell type and strain specific responses. These data raise concern that ibuprofen may increase Hirschsprung disease risk in some genetically susceptible children.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.