Age-related Changes in the Proteoglycans of Human Skin

Abstract

Dramatic changes occur in skin as a function of age, including changes in morphology, physiology, and mechanical properties. Changes in extracellular matrix molecules also occur, and these changes likely contribute to the overall age-related changes in the physical properties of skin. The major proteoglycans detected in extracts of human skin are decorin and versican. In addition, adult human skin contains a truncated form of decorin, whereas fetal skin contains virtually undetectable levels of this truncated decorin. Analysis of this molecule, herein referred to as decorunt, indicates that it is a catabolic fragment of decorin rather than a splice variant. With antibody probes to the core protein, decorunt is found to lack the carboxyl-terminal portion of decorin. Further analysis by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry shows that the carboxyl terminus of decorunt is at Phe 170 of decorin. This result indicates that decorunt represents the amino-terminal 43% of the mature decorin molecule. Such a structure is inconsistent with alternative splicing of decorin and suggests that decorunt is a catabolic fragment of decorin. A neoepitope antiserum, anti-VRKVTF, was generated against the carboxyl terminus of decorunt. This antiserum does not recognize intact decorin in any skin proteoglycan sample tested on immunoblots but recognizes every sample of decorunt tested. The results with anti-VRKVTF confirm the identification of the carboxyl terminus of decorunt. Analysis of collagen binding by surface plasmon resonance indicates that the affinity of decorunt for type I collagen is 100-fold less than that of decorin. This observation correlates with the structural analysis of decorunt, in that it lacks regions of decorin previously shown to be important for interaction with type I collagen. The detection of a catabolic fragment of decorin suggests the existence of a specific catabolic pathway for this proteoglycan. Because of the capacity of decorin to influence collagen fibrillogenesis, catabolism of decorin may have important functional implications with respect to the dermal collagen network.The mechanical properties of the dermis are determined primarily by the extracellular matrix. These mechanical properties change dramatically as a function of age (1, 2), perhaps as a direct result of the known age-related changes in the molecules of the dermal extracellular matrix. Age-related differences have been shown for fibrillar collagens (3-7), which are the major extracellular matrix components of the dermis (8). In addition to collagen, the dermal extracellular matrix also contains proteoglycans, which show age-related differences (9 -16). Perhaps related to these changes in proteoglycans are age-related increases in the water content of the dermis (11) and in the content of mobile water (17).Although dermal proteoglycans are present in much lower abundance than collagen, evidence indicates that these molecules are important in the physiology of skin. For example, the small proteogl...

Adamts5 Deletion Blocks Murine Dermal Repair through CD44-mediated Aggrecan Accumulation and Modulation of Transforming Growth Factor β1 (TGFβ1) Signaling

“…Although much interest has focused on matrix metalloproteinases (9), the ADAMTSs have now also been found to play a major role in a range of repair and regeneration processes. For example, evidence of a role for ADAMTS activity in dermal repair comes from the finding that human skin contains abundant aggrecanase-generated catabolic fragments of versican V0 and V1 (5) and that both aggrecan and versican are associated with the dermal region of the hair follicle (7). Moreover, to place dermal matrix turnover in a broader context, cleavage of the hyalectans aggrecan, versican, and brevican by one or more aggrecanases (ADAMTS1, -4, -5, -8, -9, and -15) occurs in the remodeling of cartilage (10), aorta (11,12), spinal cord (13), meniscus (14,15) intervertebral disc (16), adipose tissue (17), and brain (18).…”

Expression and localization of versican during postnatal development of rat temporomandibular joint disc

“…Similar age-related changes have been reported in several different tissues, such as human skin (Carrino et al 2000), human articular cartilage (Melching et al 1997), sheep intervertebral disc (Melrose et al 2001) and human bone (Grzesik et al 2002). These studies indicated that versican is initially the major PG at the fetal or neonatal period, and its level decreases with increasing age.…”

“…Versican/PG-M is a large chondroitin sulphate PG that was first isolated from the conditioned medium of chick embryonic and human IMR-90 lung fibroblasts (Yamagata et al 1986;Zimmermann and Ruoslahti 1989) and later detected in a variety of tissues including brain, aorta, tendon, skin and other tissues (Bratt et al 1992;Larjava et al 1992;Perides et al 1992;Bignami et al 1993;Hakkinen et al 1993;Bode-Lesniewska et al 1996;Schmalfeldt et al 1998;Carrino et al 2000;Sandy et al 2001). Versican is a modular PG, along with aggrecan, brevican and neurocan, which are characterized by the assembly of various protein modules (Iozzo and Murdoch 1996).…”

Sulfated glycosaminoglycans of the vagina and perineal skin in pre- and postmenopausal women, according to genital prolapse stage

“…Previous studies in human skin showed a decrease in GAGs according to age, being evident for HS as well as for DS [14]. In animal models, there was a total GAG reduction in the skin of adult rats compared to young rats [15].…”