Hypoxia-inducible factor-1α expression in experimental cirrhosis:: correlation with vascular endothelial growth factor expression and angiogenesis
Hypoxia-inducible factor-1α expression in experimental cirrhosis:: correlation with vascular endothelial growth factor expression and angiogenesis
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DOI：
10.1111/j.1600-0463.2007.apm_610.x
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发表时间：
2007-07-01
期刊：
影响因子：
2.8
通讯作者：
Elpek, Gulsum Ozlem
中科院分区：
文献类型：
--
作者：
Bozova, Sevgi;Elpek, Gulsum Ozlem
慢性肝损伤时，血管生成与纤维化同时发生。缺氧诱导因子-1 α（HIF-1 α）是机体内环境稳定的主要调节因子，通过调节血管内皮生长因子（VEGF）在缺氧诱导的血管生成中发挥关键作用。缺氧、血管生成和VEGF表达之间的关联已在实验性肝硬化中得到证实。然而，HIF-1 α的表达尚未报道。本研究旨在探讨HIF-1 α在实验性肝纤维化过程中的表达及其与血管生成的关系。雄性Wistar大鼠腹腔注射二乙基亚硝胺（DEN）（100 mg/kg，每周1次）诱发肝硬化。在通过光学显微镜测量之前，用抗HIF-1 α、抗VEGF和抗CD 34抗体对来自肝组织的连续切片染色。我们的结果显示，HIF-1 α的表达随着纤维化的严重程度而逐渐增加（p < 0.01）。此外，它的表达被发现与血管生成（r=0.916）和VEGF表达（r=0.969）。目前的研究表明，HIF-1 α可能有一个通过调节VEGF在实验性肝纤维化的血管生成的发展中的作用，并表明该因子可能是一个潜在的目标，在慢性炎症性疾病的肝脏血管生成的操作。
Angiogenesis progresses together with fibrogenesis during chronic liver injury. Hypoxia-inducible factor-1 alpha (HIF-1 alpha), a master regulator of homeostasis, plays a pivotal role in hypoxia-induced angiogenesis through its regulation of vascular endothelial growth factor (VEGF). The association between hypoxia, angiogenesis and VEGF expression has been demonstrated in experimental cirrhosis. However, expression of HIF-1 alpha has yet to be reported. The aim of this study was to investigate the significance of HIF-1 alpha expression during experimental liver fibrosis and the relationships between HIF-1 alpha expression, VEGF expression and angiogenesis. Cirrhosis was induced in male Wistar rats by intraperitoneal administration of diethyl nitrosamine (DEN) (100 mg/kg, once a week). The serial sections from liver tissues were stained with anti-HIF-1 alpha, anti-VEGF and anti-CD34 antibodies before being measured by light microscopy. Our results showed that HIF-1 alpha expression gradually increases according to the severity of fibrosis (p < 0.01). Moreover, its expression was found to be correlated with angiogenesis (r=0.916) and VEGF expression (r=0.969). The present study demonstrates that HIF-1 alpha might have a role in the development of angiogenesis via regulation of VEGF during experimental liver fibrogenesis and suggests that this factor could be a potential target in the manipulation of angiogenesis in chronic inflammatory diseases of the liver.