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

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.

Keywords: HUVEC; NF-κB; TNFα; inflammation; transporters.

MeSH terms

  • Amino Acid Transport Systems, Basic / agonists
  • Amino Acid Transport Systems, Basic / genetics*
  • Amino Acid Transport Systems, Basic / metabolism
  • Biological Transport / drug effects
  • Gene Expression Regulation
  • Human Umbilical Vein Endothelial Cells / cytology
  • Human Umbilical Vein Endothelial Cells / drug effects*
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • NF-kappa B p52 Subunit / agonists
  • NF-kappa B p52 Subunit / genetics*
  • NF-kappa B p52 Subunit / metabolism
  • Primary Cell Culture
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Signal Transduction
  • Transcription Factor RelB / agonists
  • Transcription Factor RelB / genetics*
  • Transcription Factor RelB / metabolism
  • Tumor Necrosis Factor-alpha / pharmacology*

Substances

  • Amino Acid Transport Systems, Basic
  • NF-kappa B p52 Subunit
  • NFKB2 protein, human
  • Protein Isoforms
  • RELB protein, human
  • SLC7A2 protein, human
  • Tumor Necrosis Factor-alpha
  • Transcription Factor RelB