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Abstract
Unwanted radiological or nuclear exposure remains a public health risk for which effective therapeutic countermeasures are lacking. Here, we evaluated the efficacy of fibroblast growth factor-2 (FGF2) in treating radiation-induced gastrointestinal syndrome (RIGS) incurred by lethal whole-body irradiation (WBI) when administered in conjunction with bone marrow transplantation (BMT). In vitro experiments indicated FGF2 treatment increased proliferation, reduced apoptosis, and upregulated AKT-GSK3β/β-catenin signaling in irradiated IEC-6 cells. We next established and analyzed mice cohorts consisting of sham irradiation (Group Sh); 12 Gy WBI (Group A); WBI with BMT (Group B); WBI with FGF2 treatment (Group F); and WBI with BMT and FGF2 treatment (Group BF). At 2 weeks post-irradiation, Group BF showed a dramatic increase in survival over all other groups. Intestinal epithelium of Group BF, but not Group B or F, showed augmented proliferation, decreased apoptosis, and preserved crypt numbers and morphology. Furthermore, Group BF maintained intestinal barrier function with minimal inflammatory disturbances in a manner comparable to Group Sh. In accordance, transcriptomic analyses showed significant upregulation of intestinal barrier and stem cell markers in Group BF relative to Groups A and B. Taken together, parenteral FGF2 synergizes with BMT to confer potent mitigation against RIGS.

Author information

Kim BH1,2,3, Jung HW1, Seo SH1, Shin H4, Kwon J5, Suh JM6,7.
1
Graduate School of Medical Science and Engineering, KAIST, Daejeon, Republic of Korea.
2
Division of Biological Warfare Preparedness and Response, Armed Forces Medical Research Institute, Daejeon, Republic of Korea.
3
Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Republic of Korea.
4
Biomedical Science and Engineering Interdisciplinary Program, KAIST, Daejeon, Republic of Korea.
5
Department of Radiation Oncology, Chungnam National University College of Medicine, Daejeon, Republic of Korea. ijeannyi@daum.net.
6
Graduate School of Medical Science and Engineering, KAIST, Daejeon, Republic of Korea. jmsuh@kaist.ac.kr.
7
Biomedical Science and Engineering Interdisciplinary Program, KAIST, Daejeon, Republic of Korea. jmsuh@kaist.ac.kr.