{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:03:28Z","timestamp":1792785808362,"version":"4.5.0"},"reference-count":61,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2024,2,20]],"date-time":"2024-02-20T00:00:00Z","timestamp":1708387200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Walgreens Boots Alliance"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,6,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>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 disorganization of elastic fibre components are key features of photoageing. Although the 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To identify, using protease cleavage site prediction, novel putative matrikines with beneficial activities for skin composition and structure.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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 characterization of peptides with differential activities.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Using this pipeline we showed that cultured fibroblasts were responsive to all applied peptides, but their associated bioactivity was sequence-dependent. Based on bioactivity, toxicity and protein source, we further characterized a combination of two novel peptides, GPKG (glycine\u2013proline\u2013lysine\u2013glycine) and LSVD (leucine\u2013serine\u2013valine\u2013aspartate), that acted in vitro to enhance the transcription of matrix \u00adorganization 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\u2019s feet and firmness in a mixed population.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/bjd\/ljae061","type":"journal-article","created":{"date-parts":[[2024,2,16]],"date-time":"2024-02-16T08:34:55Z","timestamp":1708072495000},"page":"92-106","source":"Crossref","is-referenced-by-count":15,"title":["Prediction, screening and characterization of novel bioactive tetrapeptide matrikines for skin rejuvenation"],"prefix":"10.1093","volume":"191","author":[{"given":"Nathan","family":"Jariwala","sequence":"first","affiliation":[{"name":"Division of Cell Matrix Biology and Regenerative Medicine, School of Biological Science"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matiss","family":"Ozols","sequence":"additional","affiliation":[{"name":"Division of Cell Matrix Biology and Regenerative Medicine, School of Biological Science"},{"name":"Department of Human Genetics, Wellcome Sanger Institute , Genome Campus, Hinxton , UK"},{"name":"British Heart Foundation Centre of Research Excellence, University of Cambridge , Cambridge , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Eckersley","sequence":"additional","affiliation":[{"name":"Division of Cell Matrix Biology and Regenerative Medicine, School of Biological Science"},{"name":"Division of Musculoskeletal and Dermatological 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Medicine and Health, The University of Manchester , Manchester , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"Debelle","sequence":"additional","affiliation":[{"name":"Division of Cell Matrix Biology and Regenerative Medicine, School of Biological Science"},{"name":"UMR CNRS 7369 MEDyC, Universit\u00e9 de Reims Champagne Ardenne, UFR Sciences Exactes et Naturelles , SFR CAP Sant\u00e9, Moulin de la Housse, Reims , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mike","family":"Bell","sequence":"additional","affiliation":[{"name":"No7 Beauty Company , Walgreens Boots Alliance, Nottingham , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleanor\u00a0J","family":"Bradley","sequence":"additional","affiliation":[{"name":"No7 Beauty Company , Walgreens Boots Alliance, Nottingham , 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