Fig. 1. Downregulation of chondroitin 6-sulfate is associated with epidermal hyperplasia.

a The structure of CS chains is mediated by various glycosyltransferases. The common glycosaminoglycan–protein linkage region, GlcUAβ1–3Galβ1–3Galβ1–4Xylβ1-, is built on specific serine (Ser) residue(s) of core proteins such as ACAN, VCAN, DCN, and BGN. After the linkage region is formed, the CS polymerase complex assembles the CS backbone (disaccharide repeating region). b Outline of sulfation pathways. The C6-position of the GalNAc residue in the O unit is sulfated by C6ST-1 to form the C unit. Subsequently, the C unit is converted to a D unit by uronyl 2-O-sulfotransferase UST. c Expression of CS chains in normal human skin fibroblasts (n = 3) and psoriatic fibroblasts (n = 3) was analyzed using high pressure liquid chromatography (HPLC) to measure the composition of CS-disaccharides. Sulfated CS chains, isolated from the epidermis of C6st-1 WT (n = 3), C6st-1 HE (n = 4), and C6st-1 KO mice (n = 3), were analyzed using HPLC to measure the total amount (d) and composition of CS-disaccharides (e). f Gene expression levels of CS biosynthetic enzymes in the epidermis of C6st-1 WT (n = 4-6), C6st-1 HE (n = 4-7), and C6st-1 KO mice (n = 3) were analyzed using real-time PCR. g The expression pattern of 6-O-sulfated CS (CS-C) in the tail epidermis of C6st-1 WT, C6st-1 HE, and C6st-1 KO adult mice was examined by immunohistochemical analysis using anti-keratin 14 (K14) and anti-CS-C antibody. h Hematoxylin-eosin staining of paraffin-embedded skin samples from newborn and 8-week-old C6st-1 WT, C6st-1 HE, and C6st-1 KO mouse skin. Yellow arrows indicate epidermis. i Epidermal thickness of newborn and 8-week-old C6st-1 WT, C6st-1 HE, and C6st-1 KO mice. Newborn mice, C6st-1 WT (n = 4), C6st-1 HE (n = 4), and C6st-1 KO (n = 3) ; 8-week-old mice, C6st-1 WT (n = 4), C6st-1 HE (n = 3), and C6st-1 KO (n = 4) . Statistical significance was determined using one-way ANOVA with Tukey’s HSD test.