Molecular insights into the effects of sodium hyaluronate preparations in keratinocytes

Background. Hyaluronic acid (HA) preparations are widely used in clinical practice to accelerate wound healing, but it is not clear whether HA can exert direct effects on epidermal keratinocytes. Aim. To investigate the molecular and functional changes induced by HA preparations in keratinocytes by measuring global gene expression and wound healing. Methods. Human skin keratinocytes were used for this study. They were treated with either sodium hyaluronate (SH) alone or a commercial adjuvant gel (Aminogam (R)) containing SH in combination with a pool of synthetic amino acids (L-proline, L-leucine, L-lysine and glycine). Global gene expression of nearly 55 000 transcripts was investigated with a chip array (Affymetrix Human Genome U133 2.0 Plus). Results. We found that keratinocytes expressed all major HA receptors at the transcriptional level. In a fibroblast-free system, both SH and the adjuvant gel could effectively promote wound healing of keratinocytes. Major gene expression changes induced by HA preparations involves proteolysis, proteinase inhibitors, cellular metabolism and cytoskeleton. In total, 21 genes were differentially transcribed by SH and the adjuvant gel. Conclusions. Keratinocytes represent a previously underestimated target for HA action in wound healing. HA preparations induce transcriptional changes in keratinocytes and stimulate wound closure. Furthermore, the addition of synthetic amino acids to SH induces a distinct transcriptional profile.