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Epidermal growth factor regulates hematopoietic regeneration after radiation injury.

dc.contributor.author Chao, Nelson J
dc.contributor.author Chute, JP
dc.contributor.author Deoliviera, D
dc.contributor.author Doan, Phuong Linh
dc.contributor.author Fixsen, Emma
dc.contributor.author Harris, Jeffrey R
dc.contributor.author Helms, K
dc.contributor.author Himburg, Heather
dc.contributor.author Kirsch, David Guy
dc.contributor.author Quarmyne, M
dc.contributor.author Russell, JL
dc.contributor.author Sullivan, JM
dc.coverage.spatial United States
dc.date.accessioned 2017-04-28T15:02:33Z
dc.date.available 2017-04-28T15:02:33Z
dc.date.issued 2013-03
dc.identifier https://www.ncbi.nlm.nih.gov/pubmed/23377280
dc.identifier nm.3070
dc.identifier.uri https://hdl.handle.net/10161/14156
dc.description.abstract 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.
dc.language eng
dc.relation.ispartof Nat Med
dc.relation.isversionof 10.1038/nm.3070
dc.subject Animals
dc.subject Apoptosis
dc.subject Apoptosis Regulatory Proteins
dc.subject Bone Marrow
dc.subject Bone Marrow Cells
dc.subject Cells, Cultured
dc.subject Epidermal Growth Factor
dc.subject Erlotinib Hydrochloride
dc.subject Female
dc.subject Hematopoiesis
dc.subject Hematopoietic Stem Cells
dc.subject Mice
dc.subject Mice, Inbred C57BL
dc.subject Mice, Knockout
dc.subject Protein Kinase Inhibitors
dc.subject Quinazolines
dc.subject Radiation Injuries, Experimental
dc.subject Receptor, Epidermal Growth Factor
dc.subject Regeneration
dc.subject Signal Transduction
dc.subject Tumor Suppressor Proteins
dc.subject Whole-Body Irradiation
dc.subject bcl-2 Homologous Antagonist-Killer Protein
dc.subject bcl-2-Associated X Protein
dc.title Epidermal growth factor regulates hematopoietic regeneration after radiation injury.
dc.type Journal article
pubs.author-url https://www.ncbi.nlm.nih.gov/pubmed/23377280
pubs.begin-page 295
pubs.end-page 304
pubs.issue 3
pubs.organisational-group Basic Science Departments
pubs.organisational-group Clinical Science Departments
pubs.organisational-group Duke
pubs.organisational-group Duke Cancer Institute
pubs.organisational-group Faculty
pubs.organisational-group Immunology
pubs.organisational-group Institutes and Centers
pubs.organisational-group Medicine
pubs.organisational-group Medicine, Cellular Therapy
pubs.organisational-group Medicine, Hematological Malignancies
pubs.organisational-group Pathology
pubs.organisational-group Pharmacology & Cancer Biology
pubs.organisational-group Radiation Oncology
pubs.organisational-group School of Medicine
pubs.publication-status Published
pubs.volume 19
dc.identifier.eissn 1546-170X


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