Hypoxia-inducible factor-1alpha expression in experimental cirrhosis: correlation with vascular endothelial growth factor expression and angiogenesis.
Angiogenesis progresses together with fibrogenesis during chronic liver injury. Hypoxia-inducible factor-1alpha (HIF-1alpha), 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-1alpha has yet to be reported. The aim of this study was to investigate the significance of HIF-1alpha expression during experimental liver fibrosis and the relationships between HIF-1alpha 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-1alpha, anti-VEGF and anti-CD34 antibodies before being measured by light microscopy. Our results showed that HIF-1alpha 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-1alpha 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.
Bozova
Sevgi
S
Akdeniz University, Medical School, Department of Pathology, Antalya, Turkey.
Elpek
Gülsüm Ozlem
GO
D000477:Alkylating Agents / Q000633:toxicity; D000818:Animals; D004052:Diethylnitrosamine / Q000633:toxicity; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000032:analysis / Q000378:metabolism*; D008099:Liver / Q000098:blood supply* / Q000737:chemistry; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis / Q000378:metabolism*
D000477:Alkylating Agents; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A; D004052:Diethylnitrosamine