Carnosine is an endogenous dipeptide with antioxidant and scavenger properties, shown to prevent aging and photoaging process by in vivo and in vitro models on different human tissues. Here an advanced quantitative proteomic approach (high-resolution mass spectrometry and network analyses) was applied to a 3D scaffold-free dermal spheroids model to investigate the biological responses induced by carnosine in human dermis. Primary human dermal fibroblasts from a 50-years-old donor were seeded in hanging drops to develop dermis spheroids. After treatment with 150 μM L-carnosine for 7 and 14 days, collagen type III expression was evaluated by immunofluorescence on whole mount 3D tissues in high-resolution Z-stacks. Proteomic analysis was performed by nLC MS/MS (orbitrap Fusion) after proteins extraction and trypsin digestion. Collagen III localization confirmed the preservation of dermal physiological phenotype and quantitative label free proteomics analysis provides a wide description of dermis dynamic behaviour through extracellular matrix (ECM) modulation over time. In long term culture a progressive senescent profile of the spheroids was reached with upregulation of oxidative stress proteins. Carnosine induced a modulation with a positive effect on mitochondria metabolism, ECM assembly, apoptosis and aging restoring a younger profile: 204 differentially regulated proteins increased ECM remodelling (basigin and TMSB4X), cell-matrix interactions, cellular fate and tissue architecture. ROS signalling reduction and activation of antioxidant/detoxification genes (MGST3 and GSTP1) confirmed the protection of carnosine against oxidative stress and aging. Miniaturized 3D scaffold free dermis spheroids in combination with advanced quantitative proteomics analysis provide a predictive and complete approach for human tissue profiling and personalized therapies.

ESDR286 - Oxidative Stress Modulation by Carnosine in Scaffold Free Human Dermis Spheroids Model: A Proteomic Study

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.