Novel in-silico predicted matrikines are differential mediators of in vitro and in vivo cellular metabolism

Abstract

SummaryThe 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 anin silicotoin vivodiscovery pipeline, which enables the prediction and characterisation of peptide matrikines which differentially influence cellular metabolismin vitro. We use this pipeline to further characterise a combination of two novel ECM peptide mimics (GPKG and LSVD) which actin vitroto enhance the transcription of ECM organisation and cell proliferation genes andin vivoto promote epithelial and dermal remodelling. This pipeline approach can both identify new matrikines and provide insights into the mechanisms underpinning tissue homeostasis and repair.