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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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2013
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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. |
format | Online Article Text |
id | pubmed-3594347 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
record_format | MEDLINE/PubMed |
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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