C1q and TNF related protein 1 regulates expression of inflammatory genes in vascular smooth muscle cells

Genes Genomics. 2019 Apr;41(4):397-406. doi: 10.1007/s13258-018-0770-5. Epub 2018 Nov 24.

Abstract

Background: C1q and TNF related protein 1 (C1QTNF1) is known to be associated with coronary artery diseases. However, the molecular function of C1QTNF1 on the vascular smooth muscles remains to be investigated.

Objective: This study was therefore undertaken to investigate the effect of C1QTNF1 on gene expression of human smooth muscle cells and to reveal potential molecular mechanisms mediated by C1QTNF1.

Methods: Vascular smooth muscle cells were incubated with recombinant C1QTNF1 for 16 h, followed by determining any change in mRNA expressions by Affymetrix genechip. Gene ontology (GO), KEGG pathway, and protein-protein interaction (PPI) network were analyzed in differentially expressed genes. In addition, validation of microarray data was performed using quantitative real-time PCR.

Results: The mRNA expressions of annotated 74 genes were significantly altered after incubation with recombinant C1QTNF1; 41 genes were up-regulated and 33 down-regulated. The differentially expressed genes were enriched in biological processes and KEGG pathways associated with inflammatory responses. In the PPI network analysis, IL-6, CCL2, and ICAM1 were identified as potential key genes with relatively high degree. The cluster analysis in the PPI network identified a significant module composed of upregulated genes, such as IL-6, CCL2, NFKBIA, SOD2, and ICAM1. The quantitative real-time PCR results of potential key genes were consistent with microarray data.

Conclusion: The results in the present study provide insights on the effects of C1QTNF1 on gene expression of smooth muscle cells. We believe our findings will help to elucidate the molecular mechanisms regarding the functions of C1QTNF1 on smooth muscle cells in inflammatory diseases.

Keywords: C1QTNF1; CTRP1; Gene expression; Microarray; Regulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aorta / cytology*
  • Cells, Cultured
  • Chemokine CCL2 / genetics
  • Chemokine CCL2 / metabolism
  • Gene Expression Profiling
  • Humans
  • Intercellular Adhesion Molecule-1 / genetics
  • Intercellular Adhesion Molecule-1 / metabolism
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Myocytes, Smooth Muscle / drug effects*
  • Myocytes, Smooth Muscle / metabolism
  • NF-KappaB Inhibitor alpha / genetics
  • NF-KappaB Inhibitor alpha / metabolism
  • Protein Interaction Maps
  • Proteins / pharmacology*
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase / metabolism
  • Transcriptome*

Substances

  • C1QTNF1 protein, human
  • CCL2 protein, human
  • Chemokine CCL2
  • IL6 protein, human
  • Interleukin-6
  • NFKBIA protein, human
  • Proteins
  • Intercellular Adhesion Molecule-1
  • NF-KappaB Inhibitor alpha
  • Superoxide Dismutase
  • superoxide dismutase 2