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首页> 外文期刊>Molecular and Cellular Biology >Endothelial Expression of β1 Integrin Is Required for Embryonic Vascular Patterning and Postnatal Vascular Remodeling
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Endothelial Expression of β1 Integrin Is Required for Embryonic Vascular Patterning and Postnatal Vascular Remodeling

机译：胚胎血管模式和产后血管重塑需要β1整合素的内皮表达。

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The largest subgroup of integrins is that containing the β1 subunit. β1 integrins have been implicated in a wide array of biological processes ranging from adhesion to cell growth, organogenesis, and mechanotransduction. Global deletion of β1 integrin expression results in embryonic death at ca. embryonic day 5 (E5), a developmental time point too early to determine the effects of this integrin on vascular development. To elucidate the specific role of β1 integrin in the vasculature, we conditionally deleted the β1 gene in the endothelium. Homozygous deletion of β1 integrins in the endothelium resulted in failure of normal vascular patterning, severe fetal growth retardation, and embryonic death at E9.5 to 10, although there were no overt effects on vasculogenesis. Heterozygous endothelial β1 gene deletion did not diminish fetal or postnatal survival, but it reduced β1 subunit expression in endothelial cells from adult mice by approximately 40%. These mice demonstrated abnormal vascular remodeling in response to experimentally altered in vivo blood flow and diminished vascularization in healing wounds. These data demonstrate that endothelial expression of β1 integrin is required for developmental vascular patterning and that endothelial β1 gene dosing has significant functional effects on vascular remodeling in the adult. Understanding how β1 integrin expression is modulated may have significant clinical importance.
机译：整联蛋白的最大亚组是含有β1亚基的整联蛋白。 β1整联蛋白已涉及从粘附到细胞生长，器官发生和机械转导的广泛生物学过程。 β1整合素表达的整体删除导致胚胎死亡约。胚胎第5天（E5），尚无法确定该整联蛋白对血管发育的影响的发育时间点。为了阐明β1整合素在脉管系统中的特定作用，我们有条件地删除了内皮中的β1基因。内皮中β1整合素的纯合缺失导致正常的血管形成失败，严重的胎儿发育迟缓和E9.5至10的胚胎死亡，尽管对血管生成没有明显影响。杂合内皮β1基因的缺失并没有减少胎儿或出生后的存活，但是它使成年小鼠内皮细胞中β1亚基的表达降低了约40％。这些小鼠表现出异常的血管重塑，以响应实验中体内血流的改变，并减少了伤口愈合过程中的血管形成。这些数据表明，β1整联蛋白的内皮表达是发育性血管形成所必需的，并且内皮中的β1基因给药对成年人的血管重构具有重要的功能作用。了解β1整合素表达是如何被调节的可能具有重要的临床意义。

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