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
- 1 Downloads
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.
Key WordsHUVEC TNFα NF-κB inflammation transporters
Unable to display preview. Download preview PDF.
- 2.Blundell C, Tess ER, Schanzer AS, Coutifaris C, Su EJ, Parry S, Huh D. A microphysiological model of the human placental barrier. Lab Chip. 2016;16(16):3065-3073.Google Scholar
- 3.Chang C, Liu H, Wei C, Chang L, Liang J, Bei H, Li H, Liu S, Wu Y. Tongxinluo regulates expression of tight junction proteins and alleviates endothelial cell monolayer hyperpermeability via ERK-1/2 signaling pathway in oxidized lowdensity lipoprotein-induced human umbilical vein endothelial cells. Evid. Based Complement. Alternat. Med. 2017;2017. ID 4198486. doi: 10.1155/2017/4198486.Google Scholar
- 4.Holmes RS, Spradling-Reeves KD, Cox LA. Evolution of vertebrate solute carrier family 9B genes and proteins (SLC9B): evidence for a marsupial origin for testis specific SLC9B1 from an ancestral vertebrate SLC9B2 gene. J. Phylogenetics Evol. Biol. 2016;4(3). pii: 167. doi: 10.4172/2329-9002.1000167.Google Scholar
- 6.Mishima M, Hamada T, Maharani N, Ikeda N, Onohara T, Notsu T, Ninomiya H, Miyazaki S, Mizuta E, Sugihara S, Kato M, Ogino K, Kuwabara M, Hirota Y, Yoshida A, Otani N, Anzai N, Hisatome I. Effects of uric acid on the NO production of HUVECs and its restoration by urate lowering agents. Drug Res. (Stuttg). 2016;66(5):270-274.CrossRefGoogle Scholar
- 7.Nanami M, Ookawara T, Otaki Y, Ito K, Moriguchi R, Miyagawa K, Hasuike Y, Izumi M, Eguchi H, Suzuki K, Nakanishi T. Tumor necrosis factor-alpha-induced iron sequestration and oxidative stress in human endothelial cells. Arterioscler. Thromb. Vasc. Biol. 2005;25(12):2495-2501.CrossRefPubMedGoogle Scholar
- 11.Samatov TR, Galatenko VV, Senyavina NV, Galatenko AV, Shkurnikov MYu, Tonevitskaya SA, Sakharov DA, Marx U, Ehrlich H, Schumacher U, Tonevitsky AG. miRNA-mediated expression switch of cell adhesion genes driven by microcirculation in chip. BioChip J. 2017;1-8Google Scholar
- 14.Yan CH, Yu HB, Huang MF, Li J, Zhang XL, Han YL. Tumor necrosis factor-a promote permeability of human umbilical vein endothelial cells via activating RhoA-ERK1/2 pathway. Zhonghua Xin Xue Guan Bing Za Zhi. 2011;39(6):531-537.Google Scholar
- 15.Yuen N, Lam TI, Wallace BK, Klug NR, Anderson SE, O’Donnell ME. Ischemic factor-induced increases in cerebral microvascular endothelial cell Na/H exchange activity and abundance: evidence for involvement of ERK1/2 MAP kinase. Am. J. Physiol. Cell Physiol. 2014;306(10):C931-C942.CrossRefPubMedPubMedCentralGoogle Scholar