A Novel CXCR4 antagonist enhances angiogenesis via modifying the ischaemic tissue environment.
A Novel CXCR4 antagonist enhances angiogenesis via modifying the ischaemic tissue environment.
复制标题
新型 CXCR4 拮抗剂通过改变缺血组织环境增强血管生成
DOI：
10.1111/jcmm.13150
复制
发表时间：
2017-10
影响因子：
5.3
通讯作者：
Tan Y
中科院分区：
文献类型：
--
作者：
Yan X;Dai X;He L;Ling X;Shao M;Zhang C;Wang Y;Xiao J;Cai L;Li X;Tan Y
内皮祖细胞（Endothelial progenitor cells，EPCs）通过直接参与新生血管形成和分泌促血管生成因子，在血管生成中发挥重要作用。基质细胞衍生因子1（SDF-1）及其受体CXCR 4在骨髓中EPCs在其小生境内的保留和静止中起关键作用。干扰SDF-1和CXCR 4之间的相互作用是EPC动员的有效策略。我们开发了一种新的CXCR 4拮抗剂P2 G，这是一种SDF-1β突变蛋白，对CXCR 4具有高拮抗活性，并在增强缺血性血管生成和血液灌注方面具有高效力。然而，其对缺血组织的直接影响在很大程度上仍然未知。在这项研究中，发现P2 G具有强大的能力，可以促进EPC在新血管中的浸润和掺入，增强促血管生成因子如SDF-1、血管内皮生长因子和基质金属蛋白-9的表达和功能，并激活参与血管生成的细胞信号，如增殖细胞核抗原、蛋白激酶B（Akt）、细胞外调节蛋白激酶和雷帕霉素的哺乳动物靶点。此外，P2 G可以减弱纤维化重塑，以促进缺血组织的恢复。P2 G直接增强缺血环境促进血管生成的能力提示其是治疗缺血性疾病的潜在候选者。
Endothelial progenitor cells (EPCs) play a capital role in angiogenesis via directly participating in neo‐vessel formation and secreting pro‐angiogenic factors. Stromal cell‐derived factor 1 (SDF‐1) and its receptor CXCR4 play a critical role in the retention and quiescence of EPCs within its niche in the bone marrow. Disturbing the interaction between SDF‐1 and CXCR4 is an effective strategy for EPC mobilization. We developed a novel CXCR4 antagonist P2G, a mutant protein of SDF‐1β with high antagonistic activity against CXCR4 and high potency in enhancing ischaemic angiogenesis and blood perfusion. However, its direct effects on ischaemic tissue remain largely unknown. In this study, P2G was found to possess a robust capability to promote EPC infiltration and incorporation in neo‐vessels, enhance the expression and function of pro‐angiogenic factors, such as SDF‐1, vascular endothelial growth factor and matrix metalloprotein‐9, and activate cell signals involved in angiogenesis, such as proliferating cell nuclear antigen, protein kinase B (Akt), extracellular regulated protein kinases and mammalian target of rapamycin, in ischaemic tissue. Moreover, P2G can attenuate fibrotic remodelling to facilitate the recovery of ischaemic tissue. The capability of P2G in direct augmenting ischaemic environment for angiogenesis suggests that it is a potential candidate for the therapy of ischaemia diseases.
登录
查看更多内容
影响因子：
56.9
作者：
Asahara, T;Murohara, T;Isner, JM
通讯作者：
Isner, JM
影响因子：
2.9
作者：
Mace, Kimberly A.;Yu, Diana H.;Young, David M.
通讯作者：
Young, David M.
影响因子：
3.6
作者：
Springael, JY;Le Minh, PN;Parmentier, M
通讯作者：
Parmentier, M
影响因子：
82.9
作者：
Ceradini, DJ;Kulkarni, AR;Gurtner, GC
通讯作者：
Gurtner, GC
影响因子：
15.3
作者：
Nie, Yuchun;Han, Yoon-Chi;Zou, Yong-Rui
通讯作者：
Zou, Yong-Rui