The dermis of skin is a connective tissue that contains an extensive extracellular matrix (ECM) whose biophysical properties are determined primarily by this matrix. Although collagen and elastin are the major extracellular matrix molecules of the dermis that provide skin its structural strength and elasticity, other molecular components such as proteoglycans also contribute to the overall mechanical properties of skin. Proteoglycans is one of the major ground substances in the extracellular matrix of the dermal connective tissue synthesized and secreted by dermal fibroblast.
Proteoglycans are proteins that are heavily glycosylated. The basic proteoglycan unit consists of a “core protein” with one or more covalently attached sulfated carbohydrate (glycosaminoglycan (GAG)) chains. The major biological function of proteoglycans derives from the physicochemical characteristics of the glycosaminoglycan component of the molecule, which provides hydration (due to its strong water binding capacity) and swelling pressure to the tissue enabling it to withstand compressional forces (skin’s incompressibility) as well as the viscous component of skin’s viscoelasticity when collagen fibers slide and realign in response to tensile (stretching) stress. In addition, Proteoglycans act as connective tissue organizers, influence fibroblast proliferation, differentiation and migration, and regulate collagen fibrillogenesis.
Proteoglycans can be categorized depending on the nature of their glycosaminoglycan chains. There are four types of glycosaminoglycan (GAG) found in proteoglycans: chondroitin sulfate (CS), dermatan sulfate (DS), heparan sulfate (HS), keratan sulfate (KS). Proteoglycans can also be categorized by size. Large proteoglycans include versican, perlecan, neurocan, aggrecan; Small proteoglycans include: decorin, biglycan, testican, fibromodulin, lumican. The most abundant proteoglycans in skin are decorin or decorunt (a catabolic fragment of decorin) and versican. Versican interact with elastic fibers in skin whereas decorin interacts with collagen by binding to type I collagen fibrils, and plays a role in matrix assembly and collagen fibrillogenesis thereby is crucial for robust tensile strength of skin through the establishment of a sound network of collagen fibers . Decorin also interacts with fibronectin, thrombospondin, the complement component C1q, epidermal growth factor receptor (EGFR) and transforming growth factor-beta (TGF-beta) which suggest a role in angiogenesis and skin cell renewal in response to tissue injury. Versican also have a role in cell adhesion, migration, and proliferation.
The contribution of age-related changes in skin proteoglycans to the age-related changes in the mechanical properties of skin were studied. Proteoglycans from human skin of various ages were extracted and analyzed. Samples were obtained from fetal, mature, and senescent skin. A decrease in versican and a concomitant increase in decorin was observed as a function of age. There are age-related differences in the size and polydispersity of decorin and the core proteins of decorin. The most pronounced change is the appearance in mature skin of decorunt (a catabolic fragment of decorin). Because of the known ability of decorin to influence collagen fibrillogenesis and fibril diameter, the appearance of decorunt may have a significant effect on skin elasticity and extensibility. The observation that proteoglycans in skin show dramatic age-related differences suggests that these changes may be involved in the age-related changes in the biophysical properties of skin.
Based on the immunochemical studies using monoclonal antibodies to the distinct epitope of GAG chains, an age-related common distribution pattern of GAGs in proteoglycans existed in skin. The relative amounts of specific types of glycosaminoglycans (GAG) chains in proteoglycan varied in an age- and layer-dependent manner. In the epidermis there was a notable increase in keratan sulfate beginning at age 50. Chondroitin 6-sulfate, found principally in the basal lamina, decreased after age 60. In the papillary dermis, the amount of dermatan sulfate increased after age 50, whereas the amount of a chondroitin sulfate epitope decreased with age. Thus, age-related changes in proteoglycan distribution exist and correlate with morphologic and functional changes that occur in the intrinsic process of skin aging although this study can not reveal which specific core protein (proteoglycan) is associated with the various domains of GAG chains detected.