Proline-containing tripeptides for skin health: Small tripeptides modulate both keratinocyte and fibroblast cell function

Objective: Skin is a complex tissue whose health is modulated by multiple factors. Exposure to the environment causes damage to skin cells and skin tissue. Identification of factors that can improve skin cell function potentially can prevent or reverse skin aging. Fibroblast growth factors (FGFs) induce growth of skin cells and regulate multiple genes important for skin function. However, FGFs cannot penetrate skin and thus cannot be used as therapeutic factors. Methods: Here we tested three proline-containing tripeptides for their ability to induce skin cell growth, change gene expression within these cells, and protect cells from harmful agents. We also tested the ability of one peptide to penetrate skin, a prerequisite to influence skin cells in vivo. Results: We identified three short proline-containing tripeptides that increase both fibroblast and keratinocyte cell growth, increase the abundance of COL1A1 (collagen type 1) and AQP3 (aquaporin 3) mRNA transcripts and decrease IL6 (interleukin-6) transcripts, all features of improved skin health. These tripeptides, when used as a pretreatment, prevent an increase in the abundance of MMP1 (matrix metalloprotease 1), a biomarker of skin damage when these cells are treated with an aging compound. Finally, we show that one of these tripeptides can penetrate skin. Conclusions: Proline-containing tripeptides have properties that indicate they can be used to reduce or reverse skin damage.