Epidermal Growth Factor Regulates Hematopoietic Regeneration Following Radiation Injury

The mechanisms which regulate HSC regeneration following myelosuppressive injury are not well understood. We identified epidermal growth factor (EGF) to be highly enriched in the bone marrow (BM) serum of mice bearing deletion of Bak and Bax in Tie2(+) cells (Tie2Cre;Bak1(−/−);Bax(fl/−) mice), which...

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Autores principales: Doan, Phuong L., Himburg, Heather A., Helms, Katherine, Russell, J. Lauren, Fixsen, Emma, Quarmyne, Mamle, Harris, Jeffrey R., Deoliviera, Divino, Sullivan, Julie M., Chao, Nelson J., Kirsch, David G., Chute, John P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3594347/
https://www.ncbi.nlm.nih.gov/pubmed/23377280
http://dx.doi.org/10.1038/nm.3070
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author Doan, Phuong L.
Himburg, Heather A.
Helms, Katherine
Russell, J. Lauren
Fixsen, Emma
Quarmyne, Mamle
Harris, Jeffrey R.
Deoliviera, Divino
Sullivan, Julie M.
Chao, Nelson J.
Kirsch, David G.
Chute, John P.
author_facet Doan, Phuong L.
Himburg, Heather A.
Helms, Katherine
Russell, J. Lauren
Fixsen, Emma
Quarmyne, Mamle
Harris, Jeffrey R.
Deoliviera, Divino
Sullivan, Julie M.
Chao, Nelson J.
Kirsch, David G.
Chute, John P.
author_sort Doan, Phuong L.
collection PubMed
description The mechanisms which regulate HSC regeneration following myelosuppressive injury are not well understood. We identified epidermal growth factor (EGF) to be highly enriched in the bone marrow (BM) serum of mice bearing deletion of Bak and Bax in Tie2(+) cells (Tie2Cre;Bak1(−/−);Bax(fl/−) mice), which displayed radioprotection of the HSC pool and 100% survival following lethal dose total body irradiation (TBI). BM HSCs from wild type mice expressed functional EGFR and systemic administration of EGF promoted the recovery of the HSC pool in vivo and the improved survival of mice following TBI. Conversely, administration of erlotinib, an EGFR antagonist, significantly decreased both HSC regeneration and mice survival following TBI. VavCre;EGFR(fl/+) mice also demonstrated delayed recovery of BM stem/progenitor cells following TBI compared to VavCre;EGFR(+/+) mice. Mechanistically, EGF reduced radiation-induced apoptosis of HSCs and mediated this effect via repression of the proapoptotic protein, PUMA. EGFR signaling regulates HSC regeneration following myelosuppressive injury.
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spelling pubmed-35943472013-09-01 Epidermal Growth Factor Regulates Hematopoietic Regeneration Following Radiation Injury Doan, Phuong L. Himburg, Heather A. Helms, Katherine Russell, J. Lauren Fixsen, Emma Quarmyne, Mamle Harris, Jeffrey R. Deoliviera, Divino Sullivan, Julie M. Chao, Nelson J. Kirsch, David G. Chute, John P. Nat Med Article The mechanisms which regulate HSC regeneration following myelosuppressive injury are not well understood. We identified epidermal growth factor (EGF) to be highly enriched in the bone marrow (BM) serum of mice bearing deletion of Bak and Bax in Tie2(+) cells (Tie2Cre;Bak1(−/−);Bax(fl/−) mice), which displayed radioprotection of the HSC pool and 100% survival following lethal dose total body irradiation (TBI). BM HSCs from wild type mice expressed functional EGFR and systemic administration of EGF promoted the recovery of the HSC pool in vivo and the improved survival of mice following TBI. Conversely, administration of erlotinib, an EGFR antagonist, significantly decreased both HSC regeneration and mice survival following TBI. VavCre;EGFR(fl/+) mice also demonstrated delayed recovery of BM stem/progenitor cells following TBI compared to VavCre;EGFR(+/+) mice. Mechanistically, EGF reduced radiation-induced apoptosis of HSCs and mediated this effect via repression of the proapoptotic protein, PUMA. EGFR signaling regulates HSC regeneration following myelosuppressive injury. 2013-02-03 2013-03 /pmc/articles/PMC3594347/ /pubmed/23377280 http://dx.doi.org/10.1038/nm.3070 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Doan, Phuong L.
Himburg, Heather A.
Helms, Katherine
Russell, J. Lauren
Fixsen, Emma
Quarmyne, Mamle
Harris, Jeffrey R.
Deoliviera, Divino
Sullivan, Julie M.
Chao, Nelson J.
Kirsch, David G.
Chute, John P.
Epidermal Growth Factor Regulates Hematopoietic Regeneration Following Radiation Injury
title Epidermal Growth Factor Regulates Hematopoietic Regeneration Following Radiation Injury
title_full Epidermal Growth Factor Regulates Hematopoietic Regeneration Following Radiation Injury
title_fullStr Epidermal Growth Factor Regulates Hematopoietic Regeneration Following Radiation Injury
title_full_unstemmed Epidermal Growth Factor Regulates Hematopoietic Regeneration Following Radiation Injury
title_short Epidermal Growth Factor Regulates Hematopoietic Regeneration Following Radiation Injury
title_sort epidermal growth factor regulates hematopoietic regeneration following radiation injury
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3594347/
https://www.ncbi.nlm.nih.gov/pubmed/23377280
http://dx.doi.org/10.1038/nm.3070
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