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Hypoxia‐inducible factor‐1α expression in experimental cirrhosis: correlation with vascular endothelial growth factor expression and angiogenesis
Author(s) -
BOZOVA SEVGI,
ELPEK GÜLSÜM ÖZLEM
Publication year - 2007
Publication title -
apmis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.909
H-Index - 88
eISSN - 1600-0463
pISSN - 0903-4641
DOI - 10.1111/j.1600-0463.2007.apm_610.x
Subject(s) - angiogenesis , vascular endothelial growth factor , hypoxia (environmental) , cirrhosis , hif1a , hypoxia inducible factors , medicine , endocrinology , vascular endothelial growth factor a , neovascularization , pathology , cancer research , biology , chemistry , vegf receptors , biochemistry , organic chemistry , oxygen , gene
Angiogenesis progresses together with fibrogenesis during chronic liver injury. Hypoxia‐inducible factor‐1α (HIF‐1α), 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‐1α has yet to be reported. The aim of this study was to investigate the significance of HIF‐1α expression during experimental liver fibrosis and the relationships between HIF‐1α 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‐1α, anti‐VEGF and anti‐CD34 antibodies before being measured by light microscopy. Our results showed that HIF‐1α 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‐1α 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.