https://orcid.org/0000-0002-7804-6143
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Ubaldo Armato, Ilaria Dal Prà, Discovering skin-rejuvenating matrikines: a new frontier in basic and applied dermatology, British Journal of Dermatology, Volume 191, Issue 1, July 2024, Pages 10–11, https://doi.org/10.1093/bjd/ljae100
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The functional homeostasis of living tissues relies upon the proper interactions between cells and their surrounding extracellular matrix (ECM). Crucially, the latter’s components and specific architecture mediate the respective mechanical features of tissues and organs rich in type I collagen and elastic fibres, such as the dermis, lungs and large arteries.1 Physiological and pathological remodelling generates – via the proteolysis of various ECM macromolecules – peptides named ‘matrikines’, which are endowed with either beneficial or harmful properties. These matrikines can function as growth factors or cytokines, modulating cell proliferation and/or migration, or inflammation and/or apoptosis.2 Skin’s accessibility and the profound age-related and/or pathology-induced (e.g. by ultraviolet radiation exposure) remodelling of its ECM combine to make it a model system ideal for basic and applied studies of the effects of matrikines.
In 2020, Shao et al. reported the ECM proteomes (or matrisomes) of multiple human and murine healthy tissues in a searchable database called ‘MatrisomeDB’.3 In their study, published in this issue of the BJD, Jariwala et al. took advantage of this database to try to identify potentially useful new matrikines via the integration of different methodological approaches into a pipeline.4,5 Remarkably, the authors sequentially linked artificial intelligence-based in silico bioinformatic prediction of the proteolytic cleavage sites of major ECM proteins to the analysis of the effects of the identified potential tetrapeptide matrikines, assessed via the proteomic and transcriptomic activities of cultured human dermal fibroblasts, in vivo short-term skin patch testing and a longer-lasting split-face clinical study. This pipeline approach revealed that the combination of two newly identified peptides [i.e. GPKG (glycine–proline–lysine–glycine) and LSVD (leucine–serine–valine–aspartate)] rejuvenated photoaged skin as efficiently as gold-standard all-trans retinoic acid did.4 Furthermore, the authors showed that the same matrikine duo evoked dissimilar responses in different skin types, implying the need to clarify the causes of the divergent skin reactions with a view to personalized precision medicine treatments.4
