Control of blood vessel development by SOX transcription factors

心血管疾病是澳大利亚S最大的健康问题，据估计，澳大利亚有300万人患有从高血压到心力衰竭的各种疾病。胚胎中血管发育不良会危及胚胎的存活，并使患者在出生后容易患上血管疾病。新血管的生长(血管生成)也是实体肿瘤在癌症进展过程中生长能力的重要因素。因此，在健康科学中，了解血管是如何形成和再生的是至关重要的。我们发现了一种名为Sox18的基因，它似乎通过控制内皮细胞的形成和/或性质来调节血管的发育，内皮细胞排列在血管内并使其不可渗透。到目前为止，我们的研究表明，SOX18基因缺陷的小鼠死于血管缺陷，这突显了该基因的重要性。这个项目致力于找出SOX18是如何工作的--在缺乏这种基因的小鼠身上到底出了什么问题，Sox18是否可以影响细胞培养中的内皮细胞行为，Sox18如何在内皮细胞中发挥作用，Sox18启动了哪些基因，以及Sox18在内皮细胞中与哪些基因合作。对这些问题的回答不仅将提供有关血管发育如何控制的基本信息，还将为未来可能的治疗方法播下种子，在这些疗法中，药物治疗可以刺激(如伤口愈合)或抑制(如在肿瘤进展中)血管发育。

Cardiovascular disease is Australia s greatest health problem, with an estimated 3 million Australians suffering a spectrum of conditions from hypertension through to heart failure. Improper development of blood vessels in the embryo can compromise survival of the embryo, and predispose patients to vascular disease after birth. The growth of new blood vessels (angiogenesis) is also an important factor in the ability of solid tumours to grow during the progression of cancer. It is therefore of fundamental importance in the health sciences to gain an understanding of how blood vessels form and regenerate. We discovered a gene, Sox18, that appears to regulate blood vessel development by controlling the formation and-or properties of endothelial cells, which line the blood vessels and make them impermeable. Our research so far indicates that MICE WITH DEFECTS IN SOX18 DIE FROM VASCULAR DEFECTS, underlining the importance of this gene. THIS PROJECT IS CONCERNED WITH FINDING OUT HOW SOX18 WORKS - exactly what goes wrong in mice lacking this gene, whether Sox18 can influence endothelial cell behaviour in cell culture, how Sox18 comes to be active in endothelial cells, what genes are switched on by Sox18, and what genes Sox18 co-operates with in its role in endothelial cells. The answers to these questions will not only provide fundamental basic information about how blood vessels development is controlled, but also sow the seeds for possible future therapies in which blood vessel development could be stimulated (eg in wound healing) or suppressed (eg in tumour progression) by drug treatments.