HUMAN MESANGIAL CELLS AND PERIPHERAL-BLOOD MONONUCLEAR-CELLS PRODUCE VASCULAR-PERMEABILITY FACTOR
HUMAN MESANGIAL CELLS AND PERIPHERAL-BLOOD MONONUCLEAR-CELLS PRODUCE VASCULAR-PERMEABILITY FACTOR
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DOI：
10.1038/ki.1993.337
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发表时间：
1993-11-01
影响因子：
19.6
通讯作者：
NAKAMURA, H
中科院分区：
文献类型：
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作者：
IIJIMA, K;YOSHIKAWA, N;NAKAMURA, H
血管通透性因子或血管内皮生长因子（VPF/VEGF）是一种约40 kD的二硫键连接的二聚体糖蛋白，其促进液体和蛋白质从血管渗漏。各种人肿瘤细胞系和细胞（包括胎儿血管平滑肌细胞）产生VPF/VEGF。由于肾小球系膜细胞（MC）与血管平滑肌细胞密切相关，我们研究了培养的人MC是否产生VPF/VEGF。北方印迹分析显示培养的人MC表达3.7kb的VPF/VEGF mRNA。人外周血单个核细胞（PBMC）也表达VPF/VEGF转录8.6和3.8 kb。尽管转录本的大小表明PBMC中存在独特的VPF/VEGF mRNA分子种类，但RT-PCR分析显示PBMC以及人MC表达含121、165和189个氨基酸的VPF/VEGF亚型，这意味着PBMC中不存在VPF/VEGF mRNA的独特选择性剪接产物。胎牛血清12-o-十四烷酰基-佛波醇-13-乙酸酯（TPA）可瞬时增强培养的人MC中VPF/VEGF mRNA的表达。转化生长因子-β 1至少在24小时内增强培养的人MC中VPF/VEGF mRNA的表达。地塞米松（DEX）抑制TPA诱导的VPF/VEGF mRNA表达的增加，而DEX没有改变基础水平。DEX抑制TPA诱导的VPF/VEGF mRNA表达的增加因此可能是转录控制的结果。用抗VPF/VEGF抗体免疫组化法检测培养的MC中VPF/VEGF蛋白的表达。TPA可增加MC中VPF/VEGF蛋白表达及VPF/VEGF mRNA表达。这些发现表明，培养的人MC和PBMC产生VPF/VEGF，并且它受到各种试剂的调节。由于VPF/VEGF促进血管内皮细胞的生长并增强血管通透性，因此MC和PBMC产生的VPF/VEGF可诱导肾小球内皮细胞增殖或增强肾小球毛细血管通透性。
Vascular permeability factor, or vascular endothelial growth factor (VPF/VEGF) is a disulfide-linked dimeric glycoprotein of about 40 kD that promotes fluid and protein leakage from blood vessels. Various human tumor cell lines and cells including fetal vascular smooth muscle cells produce VPF/VEGF. Since glomerular mesangial cells (MC) are closely related to vascular smooth muscle cells, we examined whether cultured human MC produce VPF/VEGF. Northern blotting analysis revealed that cultured human MC expressed a 3.7 kilobases (kb) VPF/VEGF mRNA. Human peripheral blood mononuclear cells (PBMC) also expressed VPF/VEGF transcripts of 8.6 and 3.8 kb. Although the sizes of the transcripts suggested the existence of unique molecular species of VPF/VEGF mRNA in PBMC, RT-PCR analysis revealed that PBMC as well as human MC expressed 121, 165, and 189 amino acid-containing isoforms of VPF/VEGF, implying that there are no unique alternative splicing products of VPF/VEGF mRNA in PBMC. Fetal calf serum 12-o-tetradecanoyl-phorbol-13-acetate (TPA) transiently enhanced VPF/VEGF mRNA expression in cultured human MC. Transforming growth factor-beta1 enhanced VPF/VEGF mRNA expression in cultured human MC at least within 24 hours. Dexamethasone (DEX) inhibited the TPA-induced increase in VPF/VEGF mRNA expression, whereas DEX did not change the basal level. That DEX depressed the TPA-induced increase in VPF/VEGF mRNA expression is therefore probably a result of transcriptional control. VPF/VEGF protein was detected in cultured human MC with immunoperoxidase staining using anti-VPF/VEGF antibody. TPA increased VPF/VEGF protein levels as well as those of VPF/VEGF mRNA in cultured human MC. These findings indicate that cultured human MC and PBMC produce VPF/VEGF and that it is modulated by various agents. Since VPF/VEGF promotes growth in vascular endothelial cells and enhances vascular permeability, VPF/VEGF produced by MC and PBMC may induce the proliferation of glomerular endothelial cells or enhance the permeability of glomerular capillaries.