Age-dependent alterations of decorin glycosaminoglycans in human skin

Glycosaminoglycans (GAGs) are polysacchride chains composed of repeating dissacchride units. GAGs have high degrees of heterogeneity with regard to chain length and disaccharide composition1,2. GAGs comprise hyaluronic acids and are constituents of proteoglycans. Hyaluronic acids are composed of unsulfated and branched GAGs with molecular weights ranging from 10 to 104 kDa3. Hyaluronic acids function as ground substance to fill space in extracellular matrix (ECM), are particularly abundant in skin and joints. Proteoglycans consist of sulfated GAGs covalently linked to core proteins and have diverse localizations, such as cell surface, basement membrane and ECM4,5. Interstitial proteoglycans found in ECM can be classified into large aggregated proteoglycans (LAPs) and small leucine rich proteoglycans (SLRPs). LAPs consist of large core proteins (more than 100 kDa) and numerous GAGs and usually form large aggregates with hyaluronic acids. Four LAPs, including versican, aggrecan, brevican and neurocan are found in ECM of various connective tissues5. SLRPs form a growing, heterogeneous subfamily of proteoglycans, which are able to bind with a variety of proteins, including ECM proteins, particularly type I collagen4. Decorin, the prototype of SLRP, is abundant in the dermal ECM6,7. Decorin comprises a single unbranched GAG linked to the N-terminal 4th amino acid residue of core protein. Decorin core protein binds to specific locations on the surface of type I collagen fibrils and this binding is stabilized by electrostatic interaction of the GAG chain. Decorin binding is required for appropriate assembly of collagen fibrils and inhibits cleavage of collagen fibrils by matrix metalloprotease-18,9,10. Decorin binding to type I collagen fibrils is thought to underlie the deleterious impact of decorin alterations on skin mechanical properties, which have been highlighted by studies in experimental animals and human diseases7. Decorin deficiency is thought to be a pathogeneic factor for skin manifestiations, such as bruising and hyperelasticity, of Ehlers-Danlos syndrome, which is a group of inheritable diseases affecting connective tissues11. Alterations of decorin GAG are linked to the aged appearance seen in patients with a progeroid form of Ehlers-Danlos syndrome12,13,14. Both decorin null mice and genetically engineered mice with alterations in decorin GAG display skin fragility15,16,17. Interestingly, skin fragility is also a characteristic of elderly individuals18. This observation promoted us to investigate potential age-dependent alterations of dermal interstitial proteoglycans6,19. Although several proteoglycans, including decorin, biglycan and versican, have been found in dermal ECM20,21,22,23,24,25, a comprehensive and quantitative expression profile of interstitial proteoglycans in human skin has not been reported. In this study, we systematically characterized interstitial proteoglycans with respect to mRNA, protein and GAG in sun-protected skin of young (21–30 years old) and aged (>80 years old) individuals. Our data demonstrate that decorin is the predominant type I collagen-binding proteoglycan in human dermis. In addition, our data indicate that size of decorin GAG is reduced in skin of elderly (>80 years), compared to young (21–30 years). Alterations of decorin GAG likely contribute to skin fragility of elderly people.