Angiotensin II-stimulated vascular endothelial growth factor expression in bovine retinal pericytes.

血管紧张素II 旁分泌信号 血管内皮生长因子 周细胞 内分泌学 生物 内科学 血管内皮生长因子B 北方斑点 血管内皮生长因子A 分子生物学 信使核糖核酸 化学 受体 内皮干细胞 癌症研究 基因 医学 体外 生物化学 血管内皮生长因子受体 血压
作者
A. Otani,Hitoshi Takagi,Hideyasu Oh,Kiyoshi Suzuma,Mai Matsumura,Eiji Ikeda,Yoshikazu Honda‐Okubo
出处
期刊:PubMed 卷期号:41 (5): 1192-9 被引量:110
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Angiotensin II (AII) has been shown to play a role in many vascular diseases. In the study described, the effect of AII on vascular endothelial growth factor (VEGF) expression and related intracellular signaling mechanism was investigated in bovine retinal microcapillary pericytes.Cultured bovine retinal microvascular endothelial cells and pericytes were prepared. VEGF expression was determined by Northern blot analysis and immunoprecipitation assay. Cell proliferation was assessed by DNA content growth assay. Reporter gene studies were performed to identify the AII responsible transcription-activating region of VEGF gene.Angiotensin II induced a significant increase in VEGF mRNA in a time- and dose-dependent manner. Angiotensin II type I receptor antagonist inhibited this effect. Angiotensin II activates the transcription of VEGF gene without changing the mRNA half-life, and the AII responsible region was found in the 5'-flanking region of the VEGF gene. Angiotensin II also increased the expression of c-fos and c-jun mRNA, and antisense oligonucleotides against c-Fos blocked the AII-induced VEGF mRNA expression. The conditioned media of AII-stimulated pericyte cultures had a growth-promoting effect on endothelial cells, and this effect was inhibited almost completely by VEGF neutralizing antibody.These findings suggest that AII might induce angiogenic activity through a paracrine function of VEGF in retinal microvascular cells.

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