Epidermal growth factor regulates hematopoietic regeneration after radiation injury.
Epidermal growth factor regulates hematopoietic regeneration after radiation injury.
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骨髓抑制性损伤后HSC再生的调控机制尚不清楚。我们发现表皮生长因子（EGF）在Tie 2+细胞中缺失巴克和Bax的小鼠（Tie 2Cre; Bak 1-/-; Bisfl/-小鼠）的骨髓（BM）血清中高度富集，这些小鼠显示出HSC池的辐射保护作用，并在致死剂量全身照射（TBI）后100%存活。来自野生型小鼠的BM HSC表达功能性EGFR，并且全身施用EGF促进了HSC池在体内的恢复，并且改善了TBI后小鼠的存活率。相反，EGFR拮抗剂厄洛替尼的给药显著降低了TBI后HSC再生和小鼠存活率。与VavCre;EGFR+/+小鼠相比，VavCre; EGFR fl/+小鼠还显示出在TBI后BM干细胞/祖细胞的延迟恢复。从机制上讲，EGF减少了辐射诱导的HSC凋亡，并通过抑制促凋亡蛋白PUMA介导了这一效应。EGFR信号转导调节骨髓抑制性损伤后HSC再生。
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−/−;Baxfl/− 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;EGFRfl/+ 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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影响因子：
23.9
作者：
Butler JM;Nolan DJ;Vertes EL;Varnum-Finney B;Kobayashi H;Hooper AT;Seandel M;Shido K;White IA;Kobayashi M;Witte L;May C;Shawber C;Kimura Y;Kitajewski J;Rosenwaks Z;Bernstein ID;Rafii S
通讯作者：
Rafii S
影响因子：
20.3
作者：
Ekert, Paul G.;Jabbour, Anissa M.;Vaux, David L.
通讯作者：
Vaux, David L.
影响因子：
64.5
作者：
Kiel, MJ;Yilmaz, ÖH;Morrison, SJ
通讯作者：
Morrison, SJ
影响因子：
20.3
作者：
Chute, John P.;Muramoto, Garrett G.;Chao, Nelson J.
通讯作者：
Chao, Nelson J.
影响因子：
3.7
作者：
Chen BJ;Deoliveira D;Spasojevic I;Sempowski GD;Jiang C;Owzar K;Wang X;Gesty-Palmer D;Cline JM;Bourland JD;Dugan G;Meadows SK;Daher P;Muramoto G;Chute JP;Chao NJ
通讯作者：
Chao NJ