Synergistic effect of copper and amino acid mixtures on the production of extracellular matrix proteins in skin fibroblasts

Mol Biol Rep. 2021 Apr;48(4):3277-3284. doi: 10.1007/s11033-021-06403-z. Epub 2021 May 19.

Abstract

The stimulation of extracellular matrix (ECM) protein production is an interesting target to maintain normal skin structure and delay skin aging. Copper has been shown to stimulate ECM protein synthesis by activating lysyl oxidase. Although copper increases elastin and collagen synthesis, the effect of copper and amino acid mixtures on gene expression and protein synthesis changes relating to the ECM have not been fully investigated. In this study, we showed that copper ions (Cu2+) and amino acid mixtures significantly increased the expression of genes and proteins related to the ECM in human dermal fibroblasts. The expression of genes involved in ECM production was evaluated through quantitative polymerase chain reaction in the presence of amino acid mixtures containing different Cu2+ concentrations. Cu2+ dose-dependently increased the gene expression of elastin and collagen I. In addition, a mixture of amino acids and Cu2+ increased the protein expression of elastin and collagen I. We further evaluated the effect of Cu2+ with or without amino acids. Although Cu2+ treatment increased the expression of genes encoding ECM proteins, the Cu2+ treatment without amino acids did not increase protein expression in the ECM. Our results demonstrated the synergistic effects of amino acids and a Cu2+ mixture on ECM protein synthesis in dermal fibroblasts.

Keywords: Collagen I; Copper; Elastin; Extracellular matrix; Fibroblast.

MeSH terms

  • Amino Acids / metabolism*
  • Amino Acids / pharmacology
  • Cations, Divalent
  • Cell Line
  • Collagen Type I / genetics*
  • Collagen Type I, alpha 1 Chain
  • Copper / chemistry
  • Copper / metabolism*
  • Copper / pharmacology
  • Elastin / genetics*
  • Extracellular Matrix Proteins / metabolism*
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism*
  • Gene Expression Regulation
  • Humans
  • Skin / cytology

Substances

  • Amino Acids
  • Cations, Divalent
  • Collagen Type I
  • Collagen Type I, alpha 1 Chain
  • ELN protein, human
  • Extracellular Matrix Proteins
  • Copper
  • Elastin