Preclinical murine platform to evaluate therapeutic countermeasures against radiation-induced gastrointestinal syndrome Journal Article
| Authors: | Romesser, P. B.; Kim, A. S.; Jeong, J.; Mayle, A.; Dow, L. E.; Lowe, S. W. |
| Article Title: | Preclinical murine platform to evaluate therapeutic countermeasures against radiation-induced gastrointestinal syndrome |
| Abstract: | Radiation-induced gastrointestinal syndrome (RIGS) is a limiting factor for therapeutic abdominopelvic radiation and is predicted to be a major source of morbidity in the event of a nuclear accident or radiological terrorism. In this study, we developed an in vivo mouse-modeling platform that enables spatial and temporal manipulation of potential RIGS targets in mice following whole-abdomen irradiation without the confounding effects of concomitant hematopoietic syndrome that occur following whole-body irradiation. We then tested the utility of this platform to explore the effects of transient Wnt pathway activation on intestinal regeneration and animal recovery following induction of RIGS. Our results demonstrate that intestinal epithelial suppression of adenomatous polyposis coli (Apc) mitigates RIGS lethality in vivo after lethal ionizing radiation injury-induced intestinal epithelial damage. These results highlight the potential of short-term Wnt agonism as a therapeutic target and establish a platform to evaluate other strategies to stimulate intestinal regeneration after ionizing radiation damage. © 2019 National Academy of Sciences. All rights reserved. |
| Keywords: | wnt signaling; intestinal regeneration; radiation enteritis; radiation mitigator; radiation-induced gastrointestinal syndrome |
| Journal Title: | Proceedings of the National Academy of Sciences of the United States of America |
| Volume: | 116 |
| Issue: | 41 |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Date Published: | 2019-10-08 |
| Start Page: | 20672 |
| End Page: | 20678 |
| Language: | English |
| DOI: | 10.1073/pnas.1906611116 |
| PUBMED: | 31551264 |
| PROVIDER: | scopus |
| PMCID: | PMC6789742 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 November 2019 -- Source: Scopus |
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