Vascular endothelial growth factor is a survival factor for renal tubular epithelial cells
Vascular endothelial growth factor is a survival factor for renal tubular epithelial cells
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DOI：
10.1152/ajprenal.2000.278.6.f905
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发表时间：
2000-06-01
影响因子：
4.2
通讯作者：
Power, DA
中科院分区：
文献类型：
--
作者：
Kanellis, J;Fraser, S;Power, DA
血管内皮生长因子（VEGF）主要通过“内皮细胞特异性”受体VEGFR-1（flt-1）和VEGFR-2（flk-1/KDR）作为内皮细胞有丝分裂原发挥作用。只有少数非内皮细胞具有功能性VEGF受体。因此，我们研究了大鼠肾小管上皮细胞系NRK 52-E。RT-PCR、北方印迹、Western印迹、免疫荧光和配体结合检测NRK 52-E表达VEGFR-1和VEGFR-2 mRNA和蛋白。与对照组相比，血清饥饿的NRK 52-E与VEGF孵育后[3 H]胸苷掺入量显著增加（1-10 ng/ml时为2.3倍，P < 0.05; 50-100 ng/ml时为3.3倍，P < 0.01）。与对照组相比，VEGF还保护NRK 52-E免受过氧化氢诱导的凋亡和坏死（膜联蛋白-V-FITC阳性细胞，39 vs. 54%;活细胞，50.5 vs. 39.7%）。免疫组织化学染色显示，使用各种抗体的表达在正常大鼠肾小管在体内的VEGF受体。由于VEGF诱导肾小管上皮细胞的增殖和抗凋亡反应，这些数据表明，VEGF可能作为肾小管上皮细胞在体内的存活因子。
Vascular endothelial growth factor (VEGF) acts primarily as an endothelial cell mitogen via the "endothelial cell-specific" receptors VEGFR-1 (flt-1) and VEGFR-2 (flk-1/KDR). Only a few nonendothelial cells have been shown to possess functional VEGF receptors. We therefore examined the rat renal tubular epithelial cell line NRK52-E. NRK52-E expressed VEGFR-1 and VEGFR-2 mRNA and protein by RT-PCR, Northern blotting, Western blotting, immunofluorescence, and ligand binding. Serum-starved NRK52-E incubated with VEGF showed a significant increase in [(3)H]thymidine incorporation compared with control (2.3-fold at 1-10 ng/ml, P < 0.05; 3.3-fold at 50-100 ng/ml, P < 0.01). VEGF also protected NRK52-E from hydrogen peroxide-induced apoptosis and necrosis compared with control (annexin-V-FITC-positive cells, 39 vs. 54%; viable cells, 50.5 vs. 39.7%). Immunohistochemical staining using a variety of antibodies showed expression of both VEGF receptors in normal rat renal tubules in vivo. Because VEGF induced a proliferative and an antiapoptotic response in renal tubular epithelial cells, these data suggest that VEGF may act as a survival factor for renal tubular epithelium in vivo.