A new matrikine-derived peptide up-regulates longevity genes for improving extracellular matrix architecture and connections of dermal cell with its matrix

摘要

Objective Skin extracellular matrix (ECM) is a dense and well-organized structure produced by fibroblasts. This ECM transduces environmental mechano-signals to cell nucleus through the integrin-actin complex, thus triggering ECM protein syntheses. The aim of this study was to discover a novel peptide, structurally related to dermal matrikines, that promotes syntheses of ECM components. Methods and results Screening tests with 120 peptides were carried out by using normal dermal human fibroblasts (HF). As a result, one candidate of interest was isolated, the N-Prolyl Palmitoyl Tripeptide-56 Acetate (PP56), which increases collagen and fibronectin productions at gene and/or protein levels. Using liquid chromatography-tandem mass spectrometry (LC-MS/MS), a recent and innovative analytical technology, in addition to more traditional techniques, it was showed that two metabolic pathways were significantly modulated: one for collagen production and one for actin. Moreover, this peptide up-regulated the transcription of Forkhead Box O (FOXO) and sestrin messenger RNAs (mRNA), leading to production of proteins involved into longevity and more recently in collagen production. Results Results indicated that this peptide is a potential candidate to improve ECM density and organization in a new way.