Article ; Online: Prediction, screening and characterization of novel bioactive tetra-peptide matrikines for skin rejuvenation.
The British journal of dermatology
2024
Abstract: Background: Extracellular matrices play a critical role in tissue structure and function and aberrant remodelling of these matrices is a hallmark of many age-related diseases. In skin, loss of dermal collagens and disorganisation elastic fibre ... ...
| Abstract | Background: Extracellular matrices play a critical role in tissue structure and function and aberrant remodelling of these matrices is a hallmark of many age-related diseases. In skin, loss of dermal collagens and disorganisation elastic fibre components are key features of photo-ageing. Although application of some small matrix-derived peptides to aged skin has been shown to beneficially affect in vitro cell behaviour and, in vivo, molecular architecture and clinical appearance, the discovery of new peptides has lacked a guiding hypothesis. Objectives: As endogenous matrix-derived peptides can act as cell-signalling molecules (matrikines), we hypothesised that protease cleavage site prediction could identify novel putative matrikines with beneficial activities for skin composition and structure. Methods: Here, we present an in silico (peptide cleavage prediction) to in vitro (proteomic and transcriptomic activity testing in cultured human dermal fibroblasts) to in vivo (short term patch test and longer term split-face clinical study) discovery pipeline, which enables the identification and characterisation of peptides with differential activities. Results: Using this pipeline we show that cultured fibroblasts are responsive to all applied peptides but their associated bioactivity is sequence-dependent. Based on bioactivity, toxicity and protein source we further characterised a combination of two novel peptides, GPKG and LSVD, that act in vitro to enhance the transcription of matrix organisation and cell proliferation genes and in vivo, in a short-term patch test, to promote processes associated with epithelial and dermal maintenance and remodelling. Prolonged use of a formulation containing these peptides in a split-face clinical study led to significantly improved measures of crow's feet and firmness in a mixed-ethnicity population. Conclusions: We conclude that this approach to peptide discovery and testing can identify new synthetic matrikines, providing insights into biological mechanisms of tissue homeostasis and repair and new pathways to clinical intervention. |
|---|---|
| Language | English |
| Publishing date | 2024-02-20 |
| Publishing country | England |
| Document type | Journal Article |
| ZDB-ID | 80076-4 |
| ISSN | 1365-2133 ; 0007-0963 |
| ISSN (online) | 1365-2133 |
| ISSN | 0007-0963 |
| DOI | 10.1093/bjd/ljae061 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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