Distinct Expression Patterns of Genes Coding for Biological Response Modifiers Involved in Inflammatory Responses and Development of Fibrosis in Chronic Hepatitis C: Upregulation of SMAD-6 and MMP-8 and Downregulation of CAV-1, CTGF, CEBPB, PLG, TIMP-3, MMP-1, ITGA-1, ITGA-2 and LOX

Medicina (Kaunas). 2022 Nov 27;58(12):1734. doi: 10.3390/medicina58121734.

Abstract

Background and Objectives: The aim of this study was to analyze the expression of genes on transcriptomic levels involved in inflammatory immune responses and the development of fibrosis in patients with chronic hepatitis C. Materials and Methods: Expression patterns of 84 selected genes were analyzed with real-time quantitative RT PCR arrays in the peripheral blood of treatment-naive patients with chronic hepatitis C and healthy controls. The panel included pro- and anti-fibrotic genes, genes coding for extracellular matrix (EMC) structural constituents and remodeling enzymes, cell adhesion molecules, inflammatory cytokines, chemokines and growth factors, signal transduction members of the transforming growth factor- beta (TGF-ß) superfamily, transcription factors, and genes involved in epithelial to mesenchymal transition. Results: The expression of SMAD-6 coding for a signal transduction TGF-beta superfamily member as well as MMP-8 coding for an ECM protein were significantly increased in CHC patients compared with controls. Conclusions: Chronic hepatitis C was also characterized by a significant downregulation of a set of genes including CAV-1, CTGF, TIMP-3, MMP-1, ITGA-1, LOX, ITGA-2, PLG and CEBPB encoding various biological response modifiers and transcription factors. Our results suggest that chronic hepatitis C is associated with distinct patterns of gene expression modulation in pathways associated with the regulation of immune responses and development of fibrosis.

Keywords: CAV-1; SMAD-6; fibrosis; gene expression; hepatitis C infection.

MeSH terms

  • CCAAT-Enhancer-Binding Protein-beta / genetics
  • CCAAT-Enhancer-Binding Protein-beta / metabolism
  • Down-Regulation / genetics
  • Epithelial-Mesenchymal Transition
  • Fibrosis
  • Hepatitis C, Chronic* / genetics
  • Humans
  • Immunologic Factors
  • Matrix Metalloproteinase 1 / metabolism
  • Matrix Metalloproteinase 8 / genetics
  • Matrix Metalloproteinase 8 / metabolism
  • Tissue Inhibitor of Metalloproteinase-3 / genetics
  • Tissue Inhibitor of Metalloproteinase-3 / metabolism
  • Transcription Factors / genetics
  • Transforming Growth Factor beta / metabolism
  • Up-Regulation

Substances

  • Matrix Metalloproteinase 8
  • Matrix Metalloproteinase 1
  • Tissue Inhibitor of Metalloproteinase-3
  • Transforming Growth Factor beta
  • Immunologic Factors
  • Transcription Factors
  • CEBPB protein, human
  • CCAAT-Enhancer-Binding Protein-beta