Epidermal growth factor regulates hematopoietic regeneration after radiation injury.

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Doan, PL; Himburg, HA; Helms, K; Russell, JL; Fixsen, E; Quarmyne, M; Harris, JR; Deoliviera, D; Sullivan, JM; Chao, NJ; Kirsch, DG; Chute, JP

Published Date

  • March 2013

Published In

Volume / Issue

  • 19 / 3

Start / End Page

  • 295 - 304

PubMed ID

  • 23377280

Electronic International Standard Serial Number (EISSN)

  • 1546-170X

Digital Object Identifier (DOI)

  • 10.1038/nm.3070

Language

  • eng

Conference Location

  • United States