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肿瘤坏死因子α诱导人脐静脉内皮细胞中转运蛋白基因的表达与非经典核因子κB途径的转录因子基因RELB和NFKB2的表达增强相关。

TNFα-Induced Expression of Transport Protein Genes in HUVEC Cells Is Associated with Enhanced Expression of Transcription Factor Genes RELB and NFKB2 of the Non-Canonical NF-κB Pathway.

作者信息

Knyazev E N, Mal'tseva D V, Zacharyants A A, Zakharova G S, Zhidkova O V, Poloznikov A A

机构信息

BioClinilum Research Center, Moscow, Russia.

State Research Center Institute of Biomedical Problems, Russian Academy of Sciences, Moscow, Russia.

出版信息

Bull Exp Biol Med. 2018 Apr;164(6):757-761. doi: 10.1007/s10517-018-4074-1. Epub 2018 Apr 16.

Abstract

Endothelial HUVEC cells used as an in vitro model of the endothelial monolayer in placental barrier were activated by TNFα in a dose of 2 ng/ml for 24 h. Significant changes in the expression of genes of the SLC family transport protein were observed: an increase in the expression of SLC7A2, SLC12A2, SLC9B2, SLC25A37, SLC16A9, and SLC41A2 and a decrease in the expression of SLC40A1. These transporters participate in the transport of iron, magnesium, sodium, potassium, and chloride ions, protons, and amino acids. It was also found that SLC7A2, SLC12A2, SLC9B2, SLC25A37, and SLC41A2 genes have binding sites for transcriptional factor RelB that together with NFKB2 is the main effector of the non-canonical NF-κB pathway. The expression of RELB and NFKB2 genes was also significantly enhanced in TNFα-activated HUVEC cells, which can attest to the important role of the non-canonical NF-κB pathway in the regulation of gene expression of transport proteins in response to TNFα stimulation.

摘要

用作胎盘屏障中内皮单层体外模型的内皮人脐静脉内皮细胞(HUVEC),用2 ng/ml剂量的肿瘤坏死因子α(TNFα)激活24小时。观察到溶质载体(SLC)家族转运蛋白基因表达的显著变化:溶质载体7A2(SLC7A2)、溶质载体12A2(SLC12A2)、溶质载体9B2(SLC9B2)、溶质载体25A37(SLC25A37)、溶质载体16A9(SLC16A9)和溶质载体41A2(SLC41A2)的表达增加,而溶质载体40A1(SLC40A1)的表达减少。这些转运蛋白参与铁、镁、钠、钾和氯离子、质子以及氨基酸的转运。还发现,SLC7A2、SLC12A2、SLC9B2、SLC25A37和SLC41A2基因具有转录因子RelB的结合位点,RelB与NFKB2一起是非经典NF-κB途径的主要效应因子。在TNFα激活的HUVEC细胞中,RELB和NFKB2基因的表达也显著增强,这可以证明非经典NF-κB途径在响应TNFα刺激调节转运蛋白基因表达中的重要作用。

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