Summary
The exogenous application of small peptides can beneficially affect clinical skin appearance (wrinkles) and architecture (collagen and elastic fibre deposition and epidermal thickness). However, the discovery of new bioactive peptides has not been underpinned by any guiding hypothesis. As endogenous extracellular matrix (ECM)-derived peptides produced during tissue remodelling can act as molecular signals influencing cell metabolism, we hypothesised that protease cleavage site prediction could identify putative novel matrikines with beneficial activities. Here, we present an in silico to in vivo discovery pipeline, which enables the prediction and characterisation of peptide matrikines which differentially influence cellular metabolism in vitro. We use this pipeline to further characterise a combination of two novel ECM peptide mimics (GPKG and LSVD) which act in vitro to enhance the transcription of ECM organisation and cell proliferation genes and in vivo to promote epithelial and dermal remodelling. This pipeline approach can both identify new matrikines and provide insights into the mechanisms underpinning tissue homeostasis and repair.
Competing Interest Statement
The results published in this article are covered by patents: EP4000595-A1, WO2022106054-A1; EP4000596-A1, WO2022106055-A1; EP4000597-A1, WO2022106056-A1; EP4000598-A1, WO2022106057-A1 (licensed to Boots Co. Plc. With M.B, E.J.B., Y. D, A.E, M.O. and M.J.S as authors). M.B., E.J.B, Y. D., and C. C. are employees of the No7 Beauty Company, Walgreens Boots Alliance, O.P., P.M, C.R. L.B. and A.P. are employees of Sederma and are bound by confidentiality agreements that prevent them from disclosing their competing interests in this work. L.D., A.G and L.Z. declare no competing interests.