内皮细胞在维持血管完整性、血管发生（angiogenesis）、受伤组织愈合等方面发挥着至关重要的作用。而血管形成、维持以及再造的精确调节对于正常的发育、组织受伤后愈合反应、肿瘤发生等也必不可少。在2008年8月12日出版的《发育细胞》（Developmental Cell）上，来自美国的Wang等科学家发表文章称，一种内皮细胞限制小分子RNA（microRNA）：miR-126能调节发育过程中的血管新生。
在研究中科学家发现，去除小鼠体内的目标miR-126将导致血管破裂、出血，甚至是部分胚胎死亡，其原因在于血管完整性遭到破坏，以及内皮细胞分裂增生和移动能力方面的缺陷。而生存下来的变异动物则表现出心脏血管新生方面的缺陷，并将导致心肌梗塞。发生了miR-126变异的小鼠在血管方面存在的异常似乎是血管生成因子（angiogenic growth factor）-例如VEGF和FGF等信号减少导致的。因此，miR-126能增强VEGF和FGF的前血管生成（proangiogenic）作用，并通过限制Spred-1的表达来促进血管的形成，Spred-1是一种细胞内血管新生信号的抑制子。
特定的小分子RNA是如何调节血管新生信号联级放大过程的尚不清楚，在本期《发育细胞》的另一篇文章中，来自美国和意大利的Fish等科学家表示，他们从小鼠内皮细胞中得到了一些特定的小分子RNA，这些microRNA在内皮细胞中含量很高，并且内皮细胞来源于小鼠的胚胎干细胞（embryonic stem cell ES cell）以及发育中的小鼠胚胎。结果发现，miR-126负责调节内皮细胞对VEGF的反应。除此之外，敲除斑马鱼的miR-126基因将导致胚胎发育过程中血管完整性的降低以及出血发生。miR-126的作用在于直接限制VEGF通路的负调节因子，其中包括SPRED1蛋白以及磷脂酰肌醇-3激酶调节亚基2（phosphoinositol-3 kinase regulatory subunit 2，PIK3R2/p85-β）。对于斑马鱼Spred-1表达的增加或抑制VEGF信号都将导致类似于敲除miR-126的缺陷。
科学家表示，以上发现对于多种相关疾病的治疗都有着重要意义。miRNA能调节血管完整性、血管新生，从而为调节血管形成和功能提供了新方法。（生物谷Bioon.com）
生物谷推荐原始出处：
Developmental Cell，Vol 15, 261-271, 12 August 2008，Shusheng Wang, Eric N. Olson
The Endothelial-Specific MicroRNA miR-126 Governs Vascular Integrity and Angiogenesis
Shusheng Wang,1 Arin B. Aurora,1 Brett A. Johnson,1 Xiaoxia Qi,1 John McAnally,1 Joseph A. Hill,2 James A. Richardson,1,3 Rhonda Bassel-Duby,1 and Eric N. Olson1,
1 Department of Molecular Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA
2 Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA
3 Department of Pathology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA
Endothelial cells play essential roles in maintenance of vascular integrity, angiogenesis, and wound repair. We show that an endothelial cell-restricted microRNA (miR-126) mediates developmental angiogenesis in vivo. Targeted deletion of miR-126 in mice causes leaky vessels, hemorrhaging, and partial embryonic lethality, due to a loss of vascular integrity and defects in endothelial cell proliferation, migration, and angiogenesis. The subset of mutant animals that survives displays defective cardiac neovascularization following myocardial infarction. The vascular abnormalities of miR-126 mutant mice resemble the consequences of diminished signaling by angiogenic growth factors, such as VEGF and FGF. Accordingly, miR-126 enhances the proangiogenic actions of VEGF and FGF and promotes blood vessel formation by repressing the expression of Spred-1, an intracellular inhibitor of angiogenic signaling. These findings have important therapeutic implications for a variety of disorders involving abnormal angiogenesis and vascular leakage.
Developmental Cell，Vol 15, 272-284, 12 August 2008，Jason E. Fish, Deepak Srivastava
miR-126 Regulates Angiogenic Signaling and Vascular Integrity
Jason E. Fish,1,2,3 Massimo M. Santoro,3,4,6 Sarah U. Morton,1,2,3 Sangho Yu,1,2,3 Ru-Fang Yeh,5 Joshua D. Wythe,1,2 Kathryn N. Ivey,1,2,3 Benoit G. Bruneau,1,2 Didier Y.R. Stainier,3 and Deepak Srivastava1,2,3,
Gladstone Institute of Cardiovascular Disease, San Francisco, CA 94158, USA
2 Department of Pediatrics, University of California, San Francisco, San Francisco, CA 94143, USA
3 Department of Biochemistry & Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA
4 Department of Environmental and Life Sciences, University of Piemonte Orientale, 15100 Alexandria, Italy
5 Center for Bioinformatics and Molecular Biostatistics, Department of Epidemiology & Biostatistics, University of California, San Francisco, San Francisco, CA 94107, USA
Precise regulation of the formation, maintenance, and remodeling of the vasculature is required for normal development, tissue response to injury, and tumor progression. How specific microRNAs intersect with and modulate angiogenic signaling cascades is unknown. Here, we identified microRNAs that were enriched in endothelial cells derived from mouse embryonic stem (ES) cells and in developing mouse embryos. We found that miR-126 regulated the response of endothelial cells to VEGF. Additionally, knockdown of miR-126 in zebrafish resulted in loss of vascular integrity and hemorrhage during embryonic development. miR-126 functioned in part by directly repressing negative regulators of the VEGF pathway, including the Sprouty-related protein SPRED1 and phosphoinositol-3 kinase regulatory subunit 2 (PIK3R2/p85-β). Increased expression of Spred1 or inhibition of VEGF signaling in zebrafish resulted in defects similar to miR-126 knockdown. These findings illustrate that a single miRNA can regulate vascular integrity and angiogenesis, providing a new target for modulating vascular formation and function.
