Inhibition of EphA2 by Dasatinib Suppresses Radiation-Induced Intestinal Injury
Abstract
:1. Introduction
2. Results
2.1. Radiation Exposure Increases Intestinal Injury In Vivo
2.2. IR Promotes Endothelial Permeability and Mononuclear Cells Adhesion In Vitro
2.3. IR Enhances the Expression of Eph Receptors and Their Ligands in Vascular Endothelium
2.4. Depletion of EphA2 Inhibits Permeability and Adhesion of Endothelial Cells
2.5. Dasatinib Reduces IR-Induced Permeability and Adhesion by Inhibiting EphA2
2.6. Dasatinib Downregulates Phosphorylation of EphA2, Which Prevents Vascular Barrier Disruption and Leukocyte Infiltration into the Intestine
3. Discussion
4. Materials and Methods
4.1. Cell Culture and Reagents
4.2. In Vivo Radiation Exposure and Dasatinib Treatment
4.3. Transwell Migration Assay
4.4. Adhesion of Leukocytes to Endothelial Tubes
4.5. In Vitro Permeability Assay
4.6. In Vivo Permeability Assay
4.7. Isolation of Leukocytes from the Lamina Propria and FACS Analysis
4.8. Immunohistochemistry
4.9. Immunofluorescence Staining
4.10. Real-Time PCR
4.11. Western Blotting and Immunoprecipitation Analysis
4.12. siRNA Transfection Assay
4.13. Statistical Analyses
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
Abbreviations
DST | dasatinib |
IR | irradiation |
InEpCs | human intestinal epithelial cells |
HUVEC | human umbilical vein endothelial cells |
H&E stain | hematoxylin and eosin stain |
MPO | myeloperoxidase |
AJs | adherens junctions |
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Kim, A.; Seong, K.M.; Choi, Y.Y.; Shim, S.; Park, S.; Lee, S.S. Inhibition of EphA2 by Dasatinib Suppresses Radiation-Induced Intestinal Injury. Int. J. Mol. Sci. 2020, 21, 9096. https://doi.org/10.3390/ijms21239096
Kim A, Seong KM, Choi YY, Shim S, Park S, Lee SS. Inhibition of EphA2 by Dasatinib Suppresses Radiation-Induced Intestinal Injury. International Journal of Molecular Sciences. 2020; 21(23):9096. https://doi.org/10.3390/ijms21239096
Chicago/Turabian StyleKim, Areumnuri, Ki Moon Seong, You Yeon Choi, Sehwan Shim, Sunhoo Park, and Seung Sook Lee. 2020. "Inhibition of EphA2 by Dasatinib Suppresses Radiation-Induced Intestinal Injury" International Journal of Molecular Sciences 21, no. 23: 9096. https://doi.org/10.3390/ijms21239096