Ultraviolet Irradiation Induces the Accumulation of Chondroitin Sulfate, but Not Other Glycosaminoglycans, in Human Skin

Ultraviolet (UV) light alters cutaneous structure and function. Prior work has shown loss of dermal hyaluronan after UV-irradiation of human skin, yet UV exposure increases total glycosaminoglycan (GAG) content in mouse models. To more fully describe UV-induced alterations to cutaneous GAG content, we subjected human volunteers to intermediate-term (5 doses/week for 4 weeks) or single-dose UV exposure. Total dermal uronyl-containing GAGs increased substantially with each of these regimens. We found that UV exposure substantially increased dermal content of chondroitin sulfate (CS), but not hyaluronan, heparan sulfate, or dermatan sulfate. UV induced the accumulation of both the 4-sulfated (C4S) and 6-sulfated (C6S) isoforms of CS, but in distinct distributions. Next, we examined several CS proteoglycan core proteins and found a significant accumulation of dermal and endothelial serglycin, but not of decorin or versican, after UV exposure. To examine regulation in vitro, we found that UVB in combination with IL-1α, a cytokine upregulated by UV radiation, induced serglycin mRNA in cultured dermal fibroblasts, but did not induce the chondroitin sulfate synthases. Overall, our data indicate that intermediate-term and single-dose UVB exposure induces specific GAGs and proteoglycan core proteins in human skin in vivo. These molecules have important biologic functions and contribute to the cutaneous response to UV.

[1]  G. Gibson,et al.  Molecular Interactions of MMP-13 C-Terminal Domain with Chondrocyte Proteins , 2010, Connective tissue research.

[2]  A. Utani,et al.  Elastic fiber assembly is disrupted by excessive accumulation of chondroitin sulfate in the human dermal fibrotic disease, keloid. , 2009, Biochemical and biophysical research communications.

[3]  J. Bertin,et al.  NLRP3/Cryopyrin Is Necessary for Interleukin-1β (IL-1β) Release in Response to Hyaluronan, an Endogenous Trigger of Inflammation in Response to Injury* , 2009, Journal of Biological Chemistry.

[4]  M. Dutot,et al.  High molecular weight hyaluronan decreases UVB-induced apoptosis and inflammation in human epithelial corneal cells , 2009, Molecular vision.

[5]  S. Campo,et al.  Chondroitin-4-sulphate inhibits NF-kB translocation and caspase activation in collagen-induced arthritis in mice. , 2008, Osteoarthritis and cartilage.

[6]  C. Rumio,et al.  281 Low molecular weight hyaluronic acid increases the self defence of skin epithelium by induction of β-defensin 2 via TLR2 and 4 , 2008 .

[7]  Marco Palazzo,et al.  Low Molecular Weight Hyaluronic Acid Increases the Self-Defense of Skin Epithelium by Induction of β-Defensin 2 via TLR2 and TLR4 , 2008, The Journal of Immunology.

[8]  M. Åbrink,et al.  Serotonin and histamine storage in mast cell secretory granules is dependent on serglycin proteoglycan. , 2008, The Journal of allergy and clinical immunology.

[9]  S. O. Kolset,et al.  Serglycin – Structure and biology , 2008, Cellular and Molecular Life Sciences.

[10]  H. Maibach,et al.  Hyaluronan in skin: aspects of aging and its pharmacologic modulation. , 2008, Clinics in dermatology.

[11]  Kazuyuki Sugahara,et al.  Recent Advances in the Structural Study of Functional Chondroitin Sulfate and Dermatan Sulfate in Health and Disease , 2008, Connective tissue research.

[12]  L. Trudeau,et al.  Chondroitin sulfate inhibits the nuclear translocation of nuclear factor-κB in interleukin-1β-stimulated chondrocytes , 2007 .

[13]  J. Fischer,et al.  Chronic ultraviolet B irradiation causes loss of hyaluronic acid from mouse dermis because of down-regulation of hyaluronic acid synthases. , 2007, The American journal of pathology.

[14]  P. Noble,et al.  Hyaluronan in tissue injury and repair. , 2007, Annual review of cell and developmental biology.

[15]  J. Pelletier,et al.  Biochemical basis of the effect of chondroitin sulphate on osteoarthritis articular tissues , 2007, Annals of the rheumatic diseases.

[16]  S. Yamada,et al.  Structural determination of novel sulfated octasaccharides isolated from chondroitin sulfate of shark cartilage and their application for characterizing monoclonal antibody epitopes. , 2007, Glycobiology.

[17]  J. Sleeman,et al.  Differential regulation of hyaluronan metabolism in the epidermal and dermal compartments of human skin by UVB irradiation. , 2007, The Journal of investigative dermatology.

[18]  H. Maibach,et al.  Age and skin structure and function, a quantitative approach (II): protein, glycosaminoglycan, water, and lipid content and structure , 2006, Skin research and technology : official journal of International Society for Bioengineering and the Skin (ISBS) [and] International Society for Digital Imaging of Skin (ISDIS) [and] International Society for Skin Imaging.

[19]  G. Schulze-Tanzil,et al.  Glycosaminoglycan polymerization may enable osmotically inactive Na+ storage in the skin. , 2004, American journal of physiology. Heart and circulatory physiology.

[20]  J. Schalkwijk,et al.  Human single-chain antibodies reactive with native chondroitin sulfate detect chondroitin sulfate alterations in melanoma and psoriasis. , 2004, The Journal of investigative dermatology.

[21]  H. Kitagawa,et al.  Molecular Cloning of a Chondroitin Polymerizing Factor That Cooperates with Chondroitin Synthase for Chondroitin Polymerization* , 2003, Journal of Biological Chemistry.

[22]  I. Koshiishi,et al.  Quantitative alterations of hyaluronan and dermatan sulfate in the hairless mouse dorsal skin exposed to chronic UV irradiation. , 1999, Biochimica et biophysica acta.

[23]  T. Ranheim,et al.  Stimulation of serglycin and CD44 mRNA expression in endothelial cells exposed to TNF-α and IL-1α , 1999 .

[24]  Wei Zhang,et al.  Wavelength-Specific Synergy Between Ultraviolet Radiation and Interleukin-1α in the Regulation of Matrix-Related Genes: Mechanistic Role for Tumor Necrosis Factor-α , 1999 .

[25]  M. Tykocinski,et al.  Differential effects of chondroitin sulfates A and B on monocyte and B-cell activation: evidence for B-cell activation via a CD44-dependent pathway. , 1998, Blood.

[26]  M. Malaise,et al.  Effects of chondroitin sulfate and interleukin-1 beta on human articular chondrocytes cultivated in clusters. , 1998, Osteoarthritis and cartilage.

[27]  J. Rosenbloom,et al.  UVB irradiation alters cellular responses to cytokines: role in extracellular matrix gene expression. , 1997, The Journal of investigative dermatology.

[28]  J. Uitto,et al.  Chronic sun exposure alters both the content and distribution of dermal glycosaminoglycans , 1996, The British journal of dermatology.

[29]  J. Uitto,et al.  The effect of photodamage on dermal extracellular matrix. , 1996, Clinics in dermatology.

[30]  J. Uitto,et al.  Differential expression of the versican and decorin genes in photoaged and sun-protected skin. Comparison by immunohistochemical and northern analyses. , 1995, Laboratory investigation; a journal of technical methods and pathology.

[31]  R. Mulligan,et al.  Pathway-specific regulation of the synthesis of anticoagulantly active heparan sulfate. , 1994, The Journal of biological chemistry.

[32]  A. Fourtanier,et al.  ALTERATIONS OF PROTEOGLYCANS IN ULTRAVIOLET‐IRRADIATED SKIN , 1993, Photochemistry and photobiology.

[33]  R. Mecham,et al.  Impaired elastin fiber assembly related to reduced 67-kD elastin-binding protein in fetal lamb ductus arteriosus and in cultured aortic smooth muscle cells treated with chondroitin sulfate. , 1991, The Journal of clinical investigation.

[34]  A. Caplan,et al.  Patterns of glycosaminoglycan/proteoglycan immunostaining in human skin during aging. , 1990, The Journal of investigative dermatology.

[35]  L. Kligman The ultraviolet-irradiated hairless mouse: a model for photoaging. , 1989, Journal of the American Academy of Dermatology.

[36]  E. Schwartz,et al.  Connective tissue alterations in the skin of ultraviolet irradiated hairless mice. , 1988, The Journal of investigative dermatology.

[37]  A M Kligman,et al.  The contributions of UVA and UVB to connective tissue damage in hairless mice. , 1985, The Journal of investigative dermatology.

[38]  J. Menter,et al.  UV‐INDUCED ELEVATION OF SKIN GLYCOSAMINOGLYCAN LEVELS I: RAPID MEASUREMENT OF SKIN GLYCOSAMINOGLYCANS BY TITRATION WITH ACRIDINE ORANGE * , 1983, Photochemistry and photobiology.

[39]  V. Werth,et al.  Immunologic Actions of Glycosaminoglycans in Cutaneous Lupus Erythematosus & Dermatomyositis , 2010 .

[40]  L. Trudeau,et al.  Chondroitin sulfate inhibits the nuclear translocation of nuclear factor-kappaB in interleukin-1beta-stimulated chondrocytes. , 2008, Basic & clinical pharmacology & toxicology.

[41]  R. Linhardt,et al.  Immunological activity of chondroitin sulfate. , 2006, Advances in pharmacology.

[42]  T. Ranheim,et al.  Stimulation of serglycin and CD44 mRNA expression in endothelial cells exposed to TNF-alpha and IL-1alpha. , 1999, Biochimica et biophysica acta.

[43]  V. Werth,et al.  Wavelength-specific synergy between ultraviolet radiation and interleukin-1 alpha in the regulation of matrix-related genes: mechanistic role for tumor necrosis factor-alpha. , 1999, The Journal of investigative dermatology.