Hypoxia-inducible factor-1 alpha expression in experimental cirrhosis: correlation with vascular endothelial growth factor expression and angiogenesis
APMIS, cilt.115, sa.7, ss.795-801, 2007 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 115 Sayı: 7
- Basım Tarihi: 2007
- Doi Numarası: 10.1111/j.1600-0463.2007.apm_610.x
- Dergi Adı: APMIS
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
- Sayfa Sayıları: ss.795-801
- Anahtar Kelimeler: HIF-1 alpha, VEGF, cirrhosis, angiogenesis, immunohistochemistry, LIVER-DISEASE, HEPATOCELLULAR-CARCINOMA, PARTIAL-HEPATECTOMY, INDUCED VEGF, RAT-LIVER, ACTIVATION, CELLS, REGENERATION, FIBROGENESIS, MECHANISMS
- Akdeniz Üniversitesi Adresli: Evet
Özet
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.