Hypoxia-stimulated vascular endothelial growth factor production in human nasal polyp fibroblasts -: Effect of epigallocatechin-3-gallate on hypoxia-inducible factor-1α synthesis
Hypoxia-stimulated vascular endothelial growth factor production in human nasal polyp fibroblasts -: Effect of epigallocatechin-3-gallate on hypoxia-inducible factor-1α synthesis
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DOI：
10.1001/archotol.134.5.522
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发表时间：
2008-05-01
影响因子：
--
通讯作者：
Liu, Chia-Ming
中科院分区：
文献类型：
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作者：
Lin, Sze-Kwan;Shun, Chia-Tung;Liu, Chia-Ming
目的：探讨表没食子儿茶素没食子酸酯(EGCG)对低氧诱导的鼻息肉成纤维细胞血管内皮生长因子(VEGF)合成的抑制作用。用免疫印迹法检测EGCG对低氧条件下NPF产生缺氧诱导因子(HIF)-1α(最强的血管内皮生长因子)和血管内皮生长因子(VEGF)的影响。结果：Western印迹分析显示，氯化钴诱导鼻息肉细胞HIF-1α和VEGF的合成呈时间依赖性，分别在治疗后4h和8h达到高峰。表没食子儿茶素没食子酸酯可减轻氯化钴诱导的HIF-1α水平，并通过抑制HIF-1α的合成减少氯化钴刺激的血管内皮生长因子的产生。此外，寡霉素(一种特异性的HIF-1α抑制剂)与EGCG联合使用比单独使用寡霉素或EGCG对血管内皮生长因子的合成有更严重的抑制作用。然而，协同效应似乎比他们各自行动的总和要小。免疫组织化学分析显示，NPF和单个核圆形细胞表达HIF-1α和VEGF。结论：鼻息肉成纤维细胞在低氧条件下通过分泌血管内皮生长因子促进血管生成，参与鼻息肉的发病过程。表没食子儿茶素没食子酸酯可显著减少NPF中HIF-1α和VEGF的合成。
Objective: To verify the inhibitory effects of epigallocatechin-3-gallate (EGCG) on the synthesis of hypoxia-induced vascular endothelial growth factor (VEGF) in nasal polyp fibroblasts (NPFs).Design: Eight primary cultures of NPFs were established from nasal polyps. Effects of EGCG on the production of hypoxia-inducible factor (HIF)-1 alpha (the most potent VEGF stimulant) and VEGF by NPFs under hypoxic conditions were measured by Western blot analysis. Immunohistochemical staining was used to examine the in vivo expressions of HIF-1 alpha and VEGF in 20 sections of nasal polyps.Results: Western blot analysis showed that cobalt chloride induced HIF-1 alpha and VEGF synthesis in NPFs in a time-dependent manner, reaching a plateau at 4 and 8 hours, respectively, following treatment. Epigallocatechin-3-gallate attenuated the level of HIF-1 alpha induced by cobalt chloride and also reduced cobalt chloride-stimulated VEGF production by suppressing HIF-1 alpha synthesis. Furthermore, oligomycin (a specific HIF-1 alpha inhibitor) combined with EGCG resulted in a more profound inhibition of VEGF synthesis compared with oligomycin or EGCG treatment alone. Nevertheless, the synergistic effect seemed smaller than the sum of their individual actions. Immunohistochemical analysis revealed the presence of HIF-1 alpha and VEGF in NPFs and mononuclear round cells. Intimate alignment of VEGF-positive fibroblasts and proliferating small capillaries was frequently found.Conclusions: Nasal polyp fibroblasts contribute to the pathogenesis of nasal polyps by producing VEGF to promote angiogenesis under hypoxic conditions. epigallocatechin-3-gallate substantially diminishes HIF-1 alpha and VEGF synthesis in NPFs.