Syndecans and CD44 in Normal Human Keratinocyte Cultures: Modulation with Medium Composition and All-trans Retinoic Acid

Abstract

Abstract:We investigated chosen epidermal proteoglycans in different culture models to explore their expression by keratinocytes at various states of differentiation. Fully defined conditions of our epidermal reconstructions allowed for evaluation of the proteoglycans in "normal" or "ageing"-like epidermal tissues in vitro. The "ageing"-like epidermis was characterized by the viable layers' atrophy, low proliferation rate and premature keratinisation. Expression of all studied proteoglycan genes could be detected with quantitative real-time PCR but the syndecan-4 protein wasn't observed in the reconstructed epidermis using immunohistochemistry. Treatment with all-trans retinoic acid resulted in epithelial acanthosis, combined with up-regulation of proteoglycans in the "ageing"-like culture conditions. In "normal" reconstructed epidermis, retinoids increased the syndecan-4 gene expression but down-regulated that of syndecan-1. The observed complex changes are compatible with the presumed but still poorly understood roles of various proteoglycans in epidermal differentiation. Our defined culture models are suitable for screening of pharmacological agents modulating epidermal proteoglycan expression.

Isolation of all CD44 transcripts in human epidermis and regulation of their expression by various agents

“…Their functions should be influenced not only by the peptide sequences but also by the nature, position and quantity of glycans decorating their external portions [44,[83][84][85].…”

Epidermal Hyaluronan in Barrier Alteration-Related Disease

“…Among GAGs, those with covalent link to serine residues in core-proteins give rise to proteoglycans. Heparan sulfate and chondroitin sulfate, for instance, account, respectively, for 60% and 20% of such GAGs in the epidermis [10], where they participate in formation of proteoglycans, such as glypican, syndecans (1 to 4), and versican [11][12][13]. Hyaluronan, the only non-sulfated GAG and the only GAG without link to proteins, is also found in the epidermal ECM [5].…”

SARS-CoV-2 Spike Glycoprotein Binds Heparan Sulfate Chains and N-Glycans in Psoriatic Keratinocytes: A Hypothesis.

“…GAGs are covalently linked to serine residues of a core protein as proteoglycans (PGs) through the GAG-protein linkage region tetrasaccharide (xylose, galactose, glucuronic acid, N-Acetylglucosamine), followed by repeating disaccharide units formed by alternating linked GlcA and GlcNAc [40,41], being the PGs most common the syndecan (Synd) family and CD44 [40,42]. In particular, Synd-1 ectodomain contains three extracellular sites for HS attachment and two for CHS [42,43]. In addition to HS and CHS, these HSPGs can contain N-and O-linked glycans.…”