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首页> 外文期刊>Journal of Cellular Physiology >Krüppel-like factor 4 regulates blood-tumor barrier permeability via ZO-1, occludin and claudin-5
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Krüppel-like factor 4 regulates blood-tumor barrier permeability via ZO-1, occludin and claudin-5

机译：Kruppel-like因素4调节血肿通过ZO-1屏障通透性,occludin和claudin-5

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摘要

Blood-tumor barrier (BTB) constitutes an efficient organization of tight junctions which significantly reduce permeability for chemotherapy drugs. Krüppel-like factor 4 (KLF4), a member of the Krüppel-like family, has been documented in endothelial cells and may serve as an essential regulator of endothelial barrier function. However, our knowledge about the expression and function of KLF4 in the endothelial cells of BTB still remains unclear. In this study, we sought to investigate the role of KLF4 in regulation of BTB function as well as the potential molecular mechanisms. Quantitative RT-PCR, Western blot, and immunofluorescence assays demonstrated that KLF4 was down-regulated in the glioma endothelial cells (GECs) which were obtained through endothelial cells co-cultured with glioma cells. Short hairpin RNA targeting KLF4 impaired the integrity of BTB detected by trans-endothelial electric resistance assay, and meanwhile reduced the expression of ZO-1, occludin and claudin-5, demonstrated by quantitative RT-PCR, Western blot, and immunofluorescence assays. Depletion of KLF4 increased BTB permeability to small molecules detected by permeability assays. Furthermore, luciferase assays and chromatin immunoprecipitation assays showed that KLF4 up-regulated the promoter activities and interacted with "CACCC" DNA sequence presented in the promoters of ZO-1, occludin, and claudin-5. GATA-1, GATA-6, Sp1, and Sp3 factors participated in KLF4 regulation of promoter activities through binding to the promoters of tight junctions related proteins. Collectively, our results indicated that KLF4 is a key transcriptional regulator of BTB function by regulating expressions of tight junction related proteins, which would draw growing attention to KLF4 as a potential target for glioma therapy. J. Cell. Physiol. 229: 916-926, 2014.
机译：血肿(BTB)构成一个有效的障碍组织的紧密连接显著降低渗透率为化疗药物。Kruppel-like家族的一员,一直记录在内皮细胞,可以作为内皮屏障的重要调节器函数。KLF4的表达和功能内皮细胞的BTB仍然不清楚。在这项研究中,我们试图调查中的作用监管的KLF4 BTB函数以及潜在的分子机制。rt - pcr、免疫印迹和免疫荧光化验证明KLF4衰减在神经胶质瘤内皮细胞(gec)通过内皮细胞培养获得的与神经胶质瘤细胞。KLF4 BTB检测到的完整性受损trans-endothelial电阻测定与此同时减少ZO-1的表达,occludin claudin-5,证明了定量rt - pcr、免疫印迹和免疫荧光检测。增加BTB渗透率小分子检测到渗透率化验。荧光素酶检测和染色质免疫沉淀反应化验表明,KLF4差异和启动子活动与“CACCC”DNA序列中给出ZO-1的推动者,occludin, claudin-5。GATA-1、GATA-6 Sp1, Sp3因素参与通过KLF4调控的启动子活动结合紧密连接的推动者相关的蛋白质。表明KLF4是一个关键的转录通过调节调节器BTB的功能紧密连接相关蛋白的表达,这将吸引越来越多的关注KLF4作为吗神经胶质瘤治疗的潜在目标。杂志。229:916 - 926年,2014年。

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