LB1797 Novel tetra-peptide matrikines mediate dermal and epidermal metabolism in human skin

Aberrant and progressive remodeling of the dermal extracellular matrix (ECM) as a result of intrinsic and extrinsic ageing can profoundly affect clinical skin appearance and function. Exogenous, topically applied, ECM-derived peptides (matrikines), have been used to modulate skin biology, enhancing synthesis of specific ECM proteins and reducing some clinical signs of extrinsic skin ageing. Here, for the first time, we have applied machine learning approaches proteome-wide to predict two novel peptides (GPKG and LSVD; potential cleavage products of collagen I and fibulin-1 respectively) and to assess their effects on the transcriptome and proteome of cultured human dermal fibroblasts and on the transcriptome of skin biopsies taken from volunteers. In combination, these peptides acted in vitro to significantly enhance the transcription of genes implicated in ECM organization, cell proliferation and lipid metabolism. In skin, the peptides enhanced the cutaneous expression of genes involved in antioxidant activity, skin barrier formation, and dermal ECM organization. This study demonstrates that in silicoprediction of peptide cleavage sites can identify novel, biologically active peptides which affect multiple cellular tissue processes associated with maintenance of healthy skin function, and the repair of aged and photoaged skin.