Notch-RBP-J signaling regulates the mobilization and function of endothelial progenitor cells by dynamic modulation of CXCR4 expression in mice.
Notch-RBP-J signaling regulates the mobilization and function of endothelial progenitor cells by dynamic modulation of CXCR4 expression in mice.
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Notch-RBP-J 信号通过动态调节小鼠 CXCR4 表达来调节内皮祖细胞的动员和功能
DOI：
10.1371/journal.pone.0007572
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发表时间：
2009-10-27
期刊：
影响因子：
3.7
通讯作者：
Han H
中科院分区：
文献类型：
--
作者：
Wang L;Wang YC;Hu XB;Zhang BF;Dou GR;He F;Gao F;Feng F;Liang YM;Dou KF;Han H
骨髓来源的内皮祖细胞在促进组织再生方面具有治疗潜力，但这些细胞在体内如何调节一直是难以捉摸的。在这里，我们报告RBP-J，介导Notch信号的关键转录因子，通过CXCR 4调节EPC。在小鼠部分肝切除（PHx）模型中，RBP-J缺陷EPC显示归巢和促进肝再生的能力减弱。在静息小鼠中，RBP-J的条件性缺失导致BM EPC的减少，伴随着外周血中EPC的增加。这伴随着BM中EPC上CXCR 4的下调，尽管循环中EPC上CXCR 4的表达在不存在RBP-J的情况下上调。RBP-J缺陷小鼠中的PHx诱导更强的EPC动员。在体外，RBP-J缺陷的EPC表现出较低的粘附，迁移，并在三维培养中形成血管样结构的能力。CXCR 4的过表达至少可以挽救RBP-J缺陷型EPC造成的血管形成缺陷。这些数据表明，RBP-J介导的Notch信号调节EPC动员和功能，至少部分通过动态调节CXCR 4表达。我们的研究结果不仅为EPC的调控提供了新的见解，而且对使用EPC治疗疾病的临床治疗具有重要意义。
Bone marrow (BM)-derived endothelial progenitor cells (EPC) have therapeutic potentials in promoting tissue regeneration, but how these cells are modulated in vivo has been elusive. Here, we report that RBP-J, the critical transcription factor mediating Notch signaling, modulates EPC through CXCR4. In a mouse partial hepatectomy (PHx) model, RBP-J deficient EPC showed attenuated capacities of homing and facilitating liver regeneration. In resting mice, the conditional deletion of RBP-J led to a decrease of BM EPC, with a concomitant increase of EPC in the peripheral blood. This was accompanied by a down-regulation of CXCR4 on EPC in BM, although CXCR4 expression on EPC in the circulation was up-regulated in the absence of RBP-J. PHx in RBP-J deficient mice induced stronger EPC mobilization. In vitro, RBP-J deficient EPC showed lowered capacities of adhering, migrating, and forming vessel-like structures in three-dimensional cultures. Over-expression of CXCR4 could at least rescue the defects in vessel formation by the RBP-J deficient EPC. These data suggested that the RBP-J-mediated Notch signaling regulated EPC mobilization and function, at least partially through dynamic modulation of CXCR4 expression. Our findings not only provide new insights into the regulation of EPC, but also have implications for clinical therapies using EPC in diseases.
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影响因子：
13.5
作者：
Higashiyama, Reiichi;Inagaki, Yutaka;Okazaki, Isao
通讯作者：
Okazaki, Isao
影响因子：
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作者：
Fausto, N;Campbell, JS;Riehle, KJ
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Riehle, KJ
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Matsumoto, K;Yoshitomi, H;Zaret, KS
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Zaret, KS
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Ceradini, DJ;Kulkarni, AR;Gurtner, GC
通讯作者：
Gurtner, GC
影响因子：
4.4
作者：
Han, H;Tanigaki, K;Honjo, T
通讯作者：
Honjo, T