We identified Basigin (BSG, EMMPRIN, CD147) to be induced in human epidermal keratinocytes (KC) using pro-aging stress and replicative senescence (RepSen) models. BSG is a known inducer of matrix metalloproteinases (MMPs) and its ligand S100A9 increases concomitantly with other KC senescence marker expression. Its dual nature as surface receptor and secreted protein makes it a prime candidate for initiating, promoting or sustaining cellular senescence in KC targeting many of the hallmarks of senescence (Matrix remodeling via MMP activation, being a potential member of the Senescence Associated Secretory Phenotype (SASP) and sustaining a low grade inflammation via S100A9). Studying the role of BSG in juvenile skin equivalent models (SE) we found that BSG deficient SE showed reduced collagen contraction potentially due to lack of MMP activation. Investigating SE supernatants, we found a global decrease of chemo & cytokine levels whereas secretion of Chitinase3Like1 (Chi3L1), usually reported a cancer prognostic marker and pro-proliferative factor, was strongly elevated. In creating aged SE containing 5% fluorescently labelled RepSen KC we were able to study the effect of senescent cells and BSG deficiency within the tissue microenvironment at a single cell level. In this setting we were able to show that a redox-stress response mechanism that rerouts sugar metabolism via the pentose phosphate pathway is blunted in SE containing BSG-deficient RepSen KC, whereas the expected age-related increase of lactate dehydrogenase (LDH) was missing in the absence of BSG. Our findings highlight that BSG not only affects matrix remodeling and chemokine secretion, but also metabolic adaptations to cell aging.

ESDR193 - Basigin controls matrix remodeling, the secretory phenotype and metabolic adaptations of senescent epidermal keratinocytes and their microenvironment

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.