The role of CXCL12 in the organ-specific process of artery formation
The role of CXCL12 in the organ-specific process of artery formation
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DOI：
10.1182/blood-2004-07-2563
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发表时间：
2005-04-15
期刊：
影响因子：
20.3
通讯作者：
Nagasawa, T
中科院分区：
文献类型：
--
作者：
Ara, T;Tokoyoda, K;Nagasawa, T
CXC趋化因子配体12（CXCL 12;基质细胞衍生因子-1 [SDF-1]/前B细胞生长刺激因子[PBSF]）及其受体CXCR 4对于胃肠道中的血管形成以及造血细胞的B淋巴细胞生成和骨髓定殖是必需的。然而，CXCL 12/CXCR 4在血管形成中发挥作用的机制仍然难以捉摸。在这里，我们发现了一种新的器官血管化模式，并确定了CXCL 12在这些过程中的作用。在小肠发育过程中，大的上级肠系膜动脉（SMA）与原肠周围的初级毛细血管丛之间形成许多短的相互连接的血管，它们延长并成为供应小肠的动脉。缺乏CXCL 12或CXCR 4的小鼠缺乏相互连接的血管，但具有正常的静脉网络。突变体缺乏丝状伪足的延伸和肠套叠的SMA的内皮细胞中看到野生型胚胎。CXCR 4在发育中的肠系膜中的动脉中特异性表达;并且其表达在CXCL 12（-/-）胚胎中严重降低。在内皮细胞中特异性缺失CXCR 4的小鼠显示出与在常规CXCR 4（-/-）胚胎中观察到的相同的血管缺陷。总之，CXCL 12作用于SMA的动脉内皮细胞以上调CXCR 4并以器官特异性方式介导较大动脉与邻近毛细血管丛之间的连接。(c)2005年美国血液学会。
CXC chemokine ligand 12 (CXCL12; stromal cell-derived factor-1 [SDF-1]/pre-B-cell growth-stimulating factor [PBSF]) and its receptor CXCR4 are essential for vascularization in the gastrointestinal tract as well as B lymphopoiesis and colonization of bone marrow by hematopoietic cells. However, the mechanism by which CXCL12/CXCR4 functions in blood vessel formation remains elusive. Here, we have found a novel mode of organ vascularization and determined the roles of CXCL12 in these processes. In the developing small intestine, many short interconnecting vessels form between larger superior mesenteric artery (SMA) and the neighboring primary capillary plexus surrounding the primitive gut, and they elongate and become the arteries supplying the small intestine. Mice lacking CXCL12 or CXCR4 lack the interconnecting vessels but have normal venous networks. The mutants lack filopodial extension and intussusception from endothelial cells of SMAs seen in wild-type embryos. CXCR4 is specifically expressed in arteries in the developing mesenteries; and its expression is severely reduced in CXCL12(-/-) embryos. Mice in which CXCR4 is specifically deleted in the endothelium reveal vascular defects identical to those observed in the conventional CXCR4(-/-) embryos. Together, CXCL12 acts on arterial endothelial cells of SMA to up-regulate CXCR4 and mediate the connection between the larger artery and neighboring capillary plexus in an organ-specific manner. (c) 2005 by The American Society of Hematology.