血管内皮生长因子
肝切除术
血管生成
肝再生
内科学
内分泌学
脂肪变性
内皮糖蛋白
激酶插入结构域受体
免疫组织化学
缺氧诱导因子
再生(生物学)
血管内皮生长因子A
医学
生物
血管内皮生长因子受体
切除术
外科
细胞生物学
基因
生物化学
干细胞
川地34
作者
C. Redaelli,David Semela,Francine E. Carrick,M. Ledermann,Daniel Candinas,Bernhard Sauter,Jean‐François Dufour
标识
DOI:10.1016/j.jhep.2003.10.027
摘要
Background/Aims Liver regeneration is dependent upon coordinated proliferation of hepatocytes and endothelial cells. Vascular endothelial growth factor (VEGF) promotes angiogenesis. Hepatic steatosis delays regeneration and increases liver resection morbidity. We hypothesized that VEGF overexpression stimulates hepatic regeneration. Methods Recombinant adenovirus expressing human VEGF165 or adenovirus control-vector (LacZ) were administered before 2/3 hepatectomy in lean and ob/ob mice. Galactose elimination capacity, a quantitative liver function test, was repeatedly measured before and after hepatectomy. Expression of VEGF receptors (flt1, flk1), endoglin and hypoxia inducible factor-1α (HIF-1α) was assessed by quantitative RT-PCR and for endoglin also by immunohistochemistry. Results After 2/3 hepatectomy, VEGFgene transfer increased galactose elimination capacity in lean and ob/ob mice. HIF-1α, endoglin and VEGF receptor mRNA increased during regeneration in lean but not in obese mice. Staining of endothelial cells by endoglin immunohistochemistry returned to baseline reactivity in lean mice by day 6 and remained decreased in ob/ob mice. VEGF treatment decreased HIF-1α and increased flk1 response in lean mice. Conclusions Hepatic resection elicits an angiogenic response in the remnant liver, which is impaired in case of steatosis. Adenovirus-mediated transfer of VEGF hastens functional hepatic recovery in lean, and more importantly also, in obese mice after partial hepatectomy.
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