notch-rbp-j signaling regulates the mobilization and function of endothelial progenitor cells by dynamic modulation of cxcr4 expression in micenotch-rbp-j信号调节内皮祖细胞的动员和功能的动态调制趋化因子受体cxcr4表达小鼠.pdfVIP

Notch-RBP-J Signaling Regulates the Mobilization and Function of Endothelial Progenitor Cells by Dynamic Modulation of CXCR4 Expression in Mice 1,2. 1. 1. 1. 1 1 1 Lin Wang , Yao-Chun Wang , Xing-Bin Hu , Bing-Fang Zhang , Guo-Rui Dou , Fei He , Fang Gao , 1 1 2 1 Fan Feng , Ying-Min Liang , Ke-Feng Dou *, Hua Han * 1 State Key Laboratory of Cancer Biology, Department of Medical Genetics and Developmental Biology, Xi-Jing Hospital, Fourth Military Medical University, Xi’an, China, 2 Department of Hepatic Surgery, Xi-Jing Hospital, Fourth Military Medical University, Xi’an, China Abstract 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 format