Epidermal growth factor regulates hematopoietic regeneration after radiation injury.
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The mechanisms that regulate hematopoietic stem cell (HSC) regeneration after myelosuppressive injury are not well understood. We identified epidermal growth factor (EGF) to be highly enriched in the bone marrow serum of mice bearing deletion of Bak and Bax in TIE2-expressing cells in Tie2Cre; Bak1(-/-); Bax(flox/-) mice. These mice showed radioprotection of the HSC pool and 100% survival after a lethal dose of total-body irradiation (TBI). Bone marrow HSCs from wild-type mice expressed functional EGF receptor (EGFR), and systemic administration of EGF promoted the recovery of the HSC pool in vivo and improved the survival of mice after TBI. Conversely, administration of erlotinib, an EGFR antagonist, decreased both HSC regeneration and the survival of mice after TBI. Mice with EGFR deficiency in VAV-expressing hematopoietic cells also had delayed recovery of bone marrow stem and progenitor cells after TBI. Mechanistically, EGF reduced radiation-induced apoptosis of HSCs and mediated this effect through repression of the proapoptotic protein PUMA. Our findings show that EGFR signaling regulates HSC regeneration after myelosuppressive injury.
Apoptosis Regulatory Proteins
Bone Marrow Cells
Epidermal Growth Factor
Hematopoietic Stem Cells
Mice, Inbred C57BL
Protein Kinase Inhibitors
Radiation Injuries, Experimental
Receptor, Epidermal Growth Factor
Tumor Suppressor Proteins
bcl-2 Homologous Antagonist-Killer Protein
bcl-2-Associated X Protein
Published Version (Please cite this version)10.1038/nm.3070
Publication InfoChao, Nelson J; Chute, JP; Deoliviera, D; Doan, Phuong Linh; Fixsen, Emma; Harris, Jeffrey R; ... Sullivan, JM (2013). Epidermal growth factor regulates hematopoietic regeneration after radiation injury. Nat Med, 19(3). pp. 295-304. 10.1038/nm.3070. Retrieved from http://hdl.handle.net/10161/14156.
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Donald D. and Elizabeth G. Cooke Cancer Research Professor
My research interests are in two broad areas, clinical hematopoietic stem cell and cord blood transplantation and in the laboratory studies related to graft vs. host disease and immune reconstitution. On the clinical side we are currently conducting approximately 50 different clinical protocols ranging from preparatory regimens, supportive care studies and disease specific protocols. Most of these clinical studies are centered around studies of the sources of stem cells and the methods to
Assistant Professor of Medicine
Barbara Levine University Professor
My clinical interests are the multi-modality care of patients with bone and soft tissue sarcomas and developing new sarcoma therapies. My laboratory interests include utilizing mouse models of cancer to study cancer and radiation biology in order to develop new cancer therapies in the pre-clinical setting.
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