Role for the α7β1 integrin in vascular development and integrity
Role for the α7β1 integrin in vascular development and integrity
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DOI：
10.1002/dvdy.20462
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发表时间：
2005-09-01
影响因子：
2.5
通讯作者：
Burkin, DJ
中科院分区：
文献类型：
--
作者：
Flintoff-Dye, NL;Welser, J;Burkin, DJ
α7β1整合素是一种层粘连蛋白受体，与肌肉疾病以及神经肌肉和肌腱连接的发展有关。研究表明，α7β1整合素在非骨骼肌组织中也有表达。为了确定α7整合素在胚胎发育过程中这些组织中的表达模式，采用LacZ敲除策略建立了α7整合素链基因敲除小鼠。在这些小鼠中，β-半乳糖苷酶报告了α7启动子的表达。从胚胎11.5天到胚胎14.5天，β-半乳糖苷酶在发育中的中枢和周围神经系统和血管系统中检测到。α7整合素基因的缺失导致了部分胚胎死亡。几个阿尔法7基因缺失的胚胎被鉴定为脑血管出血，并显示血管平滑肌细胞减少和脑血管形成。存活到出生的阿尔法7基因缺失小鼠表现出血管平滑肌缺陷，包括增殖和肥大。此外，在α7基因缺失小鼠的脑动脉中检测到α5和α6B整合素链的表达改变，这可能与血管表型有关。我们的结果首次证明了α7β1整合素对脑血管平滑肌细胞的募集或存活是重要的，并且该整合素在血管发育和完整性中起着重要作用。(C)2005年Wiley-Liss，Inc.
The alpha 7 beta 1 integrin is a laminin receptor that has been implicated in muscle disease and the development of neuromuscular and myotendinous junctions. Studies have shown the alpha 7 beta 1 integrin is also expressed in nonskeletal muscle tissues. To identify the expression pattern of the alpha 7 integrin in these tissues during embryonic development, alpha 7 integrin chain knockout mice were generated by a LacZ knockin strategy. In these mice, expression from the alpha 7 promoter is reported by beta-galactosidase. From embryonic day (ED) 11.5 to ED14.5, beta-galactosidase was detected in the developing central and peripheral nervous systems and vasculature. The loss of the alpha 7 integrin gene resulted in partial embryonic lethality. Several alpha 7 null embryos were identified with cerebrovascular hemorrhages and showed reduced vascular smooth muscle cells and cerebral vascularization. The alpha 7 null mice that survived to birth exhibited vascular smooth muscle defects, including hyperplasia and hypertrophy. In addition, altered expression of alpha 5 and alpha 6B integrin chains was detected in the cerebral arteries of alpha 7 null mice, which may contribute to the vascular phenotype. Our results demonstrate for the first time that the alpha 7 beta 1 integrin is important for the recruitment or survival of cerebral vascular smooth muscle cells and that this integrin plays an important role in vascular development and integrity. (c) 2005 Wiley-Liss, Inc.