Amino acid and hyaluronic acid mixtures differentially regulate extra cellular matrix genes in cultured human fibroblasts

J Biol Regul Homeost Agents. 2018 May-Jun;32(3):517-527.


The aim of this screening study was to evaluate the efficacy of different proprietary mixtures of amino acid and hyaluronic acid (HA) in stimulating the production of extracellular matrix (ECM) components, particularly the neo-synthesis of elastin, and in promoting a more efficient deposition of elastic fibres (elastogenesis), while at the same time maintaining the stimulation of collagen. The study has allowed identification of the optimal ratios between the amino acids (AA) for the production of collagen and elastin. Human primary dermal fibroblasts from a 44-year-old female donor were used as a test system in an experimental design based on the evaluation of the expression of relevant ECM genes using a transcriptomic dynamic approach. The expression of ECM genes was evaluated by RTqPCR from 24 to 120 hours in the presence of the test items. Moreover, the production of ECM proteins was verified by Western blot analysis after a 120 h treatment period. In addition to elastin, collagen IV, a fundamental structural component of the basal lamina responsible for epithelial and connective tissue anchoring, was analysed as potential target for the modulation of ECM protein production by human fibroblast. The first phase of the study demonstrated that alanine and valine are essential to promote production of elastin, of which they are important constituents. The second phase of the study, which was conducted to clarify the interactions between the different clusters of AA, demonstrated that it is necessary to choose a mixture that contains specific amounts of amino acids of both proteins, collagen and elastin, to give a significant response and a significant production of both. This also proves the existence of a ratio between the 2 clusters (AA elastin/AA collagen) that guarantees an adequate and balanced response to gene expression and production by fibroblasts, collagen and elastin. The study has allowed identification of the optimal ratios between the AA for the production of collagen and elastin.

MeSH terms

  • Adult
  • Amino Acids / pharmacology*
  • Cells, Cultured
  • Extracellular Matrix / metabolism*
  • Extracellular Matrix Proteins / biosynthesis*
  • Female
  • Fibroblasts / metabolism*
  • Humans
  • Hyaluronic Acid / pharmacology*


  • Amino Acids
  • Extracellular Matrix Proteins
  • Hyaluronic Acid