美国印第安纳大学医学院的科学家日前发现二肽基肽酶4能够负性调控集落刺激因子的活性并刺激造血作用,表明了其临床潜在应用价值。

-2012年12月《自然-医学》


中文翻译


【题目】二肽基肽酶4负调控集落刺激因子活性并刺激造血作用

【译文】放射、化疗或造血干细胞(HSC)移植后造血作用恢复的增强是临床相关的。二肽基肽酶(DPP4)能够作用于多种底物,包括趋化因子间质细胞衍生因子1(SDF-1)。实验过程中表明抑制DPP4会增强SDF-1介导的祖细胞生存、体外细胞因子扩展以及返镀频率,我们出乎意料的发现DPP4在调控集落刺激因子(CSF)活性中具有更广泛的作用。DPP4在CSF粒细胞-巨噬细胞(GM)-CSF、G-CSF、白介素-3 (IL-3)和促红细胞生成素的N末端内酶切,并降低它们的活性。Dpp4敲除或DPP4抑制在体内或体外情况下都能增强CSF活性。相对全长人GM-CSF,DPP4截短的GM-CSF活性减少在机制上与对受体结合亲和力的影响、GM-CSF受体低聚化的诱导以及信号传导能力相关。放射或化疗后小鼠的造血作用在Dpp4−/−小鼠或口服活化Dpp4抑制剂的小鼠中增强。 小鼠中DPP4抑制增强移植物移入而不会妥协HSC功能,表明这种方法具有潜在临床效用。

英文原稿


[Title]: Dipeptidylpeptidase 4 negatively regulates colony-stimulating factor activity and stress hematopoiesis

[Authors]:Hal E Broxmeyer,1, 5 Jonathan Hoggatt,1, 4, 5 Heather A O’Leary,1, 5 Charlie Mantel,1 Brahmananda R Chitteti,2 Scott Cooper,1 Steven Messina-Graham,1 Giao Hangoc,1 Sherif Farag,2 Sara L Rohrabaugh,1 Xuan Ou,1 Jennifer Speth,1 Louis M Pelus,1 Edward F Srour1, 2, 3 & Timothy B Campbell1, 4

[Abstract]Enhancement of hematopoietic recovery after radiation, chemotherapy, or hematopoietic stem cell (HSC) transplantation is clinically relevant. Dipeptidylpeptidase (DPP4) cleaves a wide variety of substrates, including the chemokine stromal cell-derived factor-1 (SDF-1). In the course of experiments showing that inhibition of DPP4 enhances SDF-1–mediated progenitor cell survival, ex vivo cytokine expansion and replating frequency, we unexpectedly found that DPP4 has a more general role in regulating colony-stimulating factor (CSF) activity. DPP4 cleaved within the N-termini of the CSFs granulocyte-macrophage (GM)-CSF, G-CSF, interleukin-3 (IL-3) and erythropoietin and decreased their activity. Dpp4 knockout or DPP4 inhibition enhanced CSF activities both in vitro and in vivo. The reduced activity of DPP4-truncated versus full-length human GM-CSF was mechanistically linked to effects on receptor-binding affinity, induction of GM-CSF receptor oligomerization and signaling capacity. Hematopoiesis in mice after radiation or chemotherapy was enhanced in Dpp4−/− mice or mice receiving an orally active DPP4 inhibitor. DPP4 inhibition enhanced engraftment in mice without compromising HSC function, suggesting the potential clinical utility of this approach.

原文地址

http://www.nature.com/nm/journal/v18/n12/abs/nm.2991.html

本站声明: 生物文库所有文章欢迎转载,所有文章未说明,均属于原创,转载均请注明出处。
本文链接: http://www.bioku.cn/201302/nature-medicine-dipeptidylpeptidase-4-colony-stimulating-factor-hematopoiesis/
版权所有: 生物文库 - 生物医学、生物技术核心期刊文摘

留言


9 − 八 =


沪ICP备12028140号
点击这里给我发消息   点击这里给我发消息