Format

Send to

Choose Destination
Cell Death Dis. 2018 Mar 7;9(3):383. doi: 10.1038/s41419-018-0421-4.

Synergistic actions of FGF2 and bone marrow transplantation mitigate radiation-induced intestinal injury.

Author information

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.

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.

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center