Abstract
Several changes in skin appearance including loss of elasticity and wrinkle formation are associated with alterations in the composition of the dermal extracellular matrix. They are induced by intrinsic aging or by environmental factors such as UV light referred to as photoaging. A general characteristic in the histology of photoaged skin is the accumulation of elastotic material suggesting impaired formation and/or massive breakdown of elastic fibres. In order to shed light on some of the underlying mechanisms we tracked two of the major players in elastic fibre formation in different skin conditions: EBP (elastin binding protein), a regulator of elastic fibre assembly and VER (versican), a component of functional elastic fibres as well as non-functional elastotic material. Using quantitative RT-PCR on skin biopsies we found that the expression levels of VER and EBP were unaltered during intrinsic skin aging. Upon acute UV stress however, VER and EBP showed different regulation patterns: VER mRNA increased after 6 h and was further up-regulated until 24 h. The EBP mRNA by contrast was reduced after 6 h but showed massive induction at 24 h after acute UV stress. In chronically sun-exposed skin, VER protein was accumulated similar to elastotic material in the extracellular space, whereas its mRNA level was consistently reduced compared to sun-protected skin. The EBP mRNA by contrast showed slightly increased expression levels in the sun-exposed area compared to its sun-protected counterpart. Based on these data we propose a model which may help to explain parts of the mechanisms leading to the formation of elastotic masses. We further hypothesize that the presence of elastotic material triggers some yet unknown feedback mechanism(s) resulting in altered expression patterns of VER and EBP in chronically sun-exposed skin.
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Aspberg A, Adam S, Kostka G et al (1999) Fibulin-1 is a ligand for the C-type lectin domains of aggrecan and versican. J Biol Chem 274:20444–20449. doi:10.1074/jbc.274.29.20444
Bernstein EF, Fisher LW, Li K et al (1995) Differential expression of the versican and decorin genes in photoaged and sun-protected skin. Comparison by immunohistochemical and northern analyses. Lab Invest 72:662–669
Carrino DA, Sorrell JM, Caplan AI (2000) Age-related changes in the proteoglycans of human skin. Arch Biochem Biophys 373:91–101. doi:10.1006/abbi.1999.1545
Cattaruzza S, Schiappacassi M, Ljungberg-Rose A et al (2002) Distribution of PG-M/versican variants in human tissues and de novo expression of isoform V3 upon endothelial cell activation, migration, and neoangiogenesis in vitro. J Biol Chem 277:47626–47635. doi:10.1074/jbc.M206521200
Chen VL, Fleischmajer R, Schwartz E et al (1986) Immunochemistry of elastotic material in sun-damaged skin. J Invest Dermatol 87:334–337. doi:10.1111/1523-1747.ep12524421
Daly CH, Odland GF (1979) Age-related changes in the mechanical properties of human skin. J Invest Dermatol 73:84–87. doi:10.1111/1523-1747.ep12532770
Dours-Zimmermann MT, Zimmermann DR (1994) A novel glycosaminoglycan attachment domain identified in two alternative splice variants of human versican. J Biol Chem 269:32992–32998
Evanko SP, Angello JC, Wight TN (1999) Formation of hyaluronan- and versican-rich pericellular matrix is required for proliferation and migration of vascular smooth muscle cells. Arterioscler Thromb Vasc Biol 19:1004–1013
Faris B, Tan OT, Toselli P et al (1992) Long-term neonatal rat aortic smooth muscle cell cultures: a model for the tunica media of a blood vessel. Matrix 12:185–188
Hasegawa K, Yoneda M, Kuwabara H et al (2007) Versican, a major hyaluronan-binding component in the dermis, loses its hyaluronan-binding ability in solar elastosis. J Invest Dermatol 127:1657–1663
Hinek A, Rabinovitch M (1994) 67-kD elastin-binding protein is a protective “companion” of extracellular insoluble elastin and intracellular tropoelastin. J Cell Biol 126:563–574. doi:10.1083/jcb.126.2.563
Hinek A, Mecham RP, Keeley F et al (1991) 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. J Clin Invest 88:2083–2094. doi:10.1172/JCI115538
Hinek A, Boyle J, Rabinovitch M (1992) Vascular smooth muscle cell detachment from elastin and migration through elastic laminae is promoted by chondroitin sulfate-induced “shedding” of the 67-kDa cell surface elastin binding protein. Exp Cell Res 203:344–353. doi:10.1016/0014-4827(92)90008-V
Hinek A, Wrenn DS, Mecham RP et al (1988) The elastin receptor: a galactoside-binding protein. Science 239:1539–1541. doi:10.1126/science.2832941
Isogai Z, Aspberg A, Keene DR et al (2002) Versican interacts with fibrillin-1 and links extracellular microfibrils to other connective tissue networks. J Biol Chem 277:4565–4572. doi:10.1074/jbc.M110583200
Ito K, Shinomura T, Zako M et al (1995) Multiple forms of mouse PG-M, a large chondroitin sulfate proteoglycan generated by alternative splicing. J Biol Chem 270:958–965. doi:10.1074/jbc.270.2.958
Knudson CB, Knudson W (1993) Hyaluronan-binding proteins in development, tissue homeostasis, and disease. FASEB J 7:1233–1241
Lemire JM, Covin CW, White S et al (1994) Characterization of cloned aortic smooth muscle cells from young rats. Am J Pathol 144:1068–1081
Lemire JM, Potter-Perigo S, Hall KL (1996) Distinct rat aortic smooth muscle cells differ in versican/PG-M expression. Arterioscler Thromb Vasc Biol 16:821–829
Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)). Methods Methods 25:402–408
Mecham RP, Hinek A, Entwistle R et al (1989) Elastin binds to a multifunctional 67-kilodalton peripheral membrane protein. Biochemistry 28:3716–3722. doi:10.1021/bi00435a014
Montagna W, Kirchner S, Carlisle K (1989) Histology of sun-damaged human skin. J Am Acad Dermatol 21:907–918
Oikarinen A, Kallioinen M (1989) A biochemical and immunohistochemical study of collagen in sun-exposed and protected skin. Photodermatol 6:24–31
Oksala O, Salo T, Tammi R et al (1995) Expression of proteoglycans and hyaluronan during wound healing. J Histochem Cytochem 43:125–135
Olin AI, Morgelin M, Sasaki T et al (2001) The proteoglycans aggrecan and Versican form networks with fibulin-2 through their lectin domain binding. J Biol Chem 276:1253–1261. doi:10.1074/jbc.M006783200
Pierce GF, Vande Berg J, Rudolph R et al (1991) Platelet-derived growth factor-BB and transforming growth factor beta 1 selectively modulate glycosaminoglycans, collagen, and myofibroblasts in excisional wounds. Am J Pathol 138:629–646
Richard S, Querleux B, Bittoun J et al (1993) Characterization of the skin in vivo by high resolution magnetic resonance imaging: water behavior and age-related effects. J Invest Dermatol 100:705–709. doi:10.1111/1523-1747.ep12472356
Romeis B (1989) Mikroskopische Technik, 17th edn. Urban & Schwarzenberg, Munich
Schwartz E, Cruickshank FA, Christensen CC et al (1993) Collagen alterations in chronically sun-damaged human skin. Photochem Photobiol 58:841–844. doi:10.1111/j.1751-1097.1993.tb04981.x
Sheng W, Wang G, Wang Y et al (2005) The roles of versican V1 and V2 isoforms in cell proliferation and apoptosis. Mol Biol Cell 16:1330–1340. doi:10.1091/mbc.E04-04-0295
Sorrell JM, Carrino DA, Baber MA et al (1999) A monoclonal antibody which recognizes a glycosaminoglycan epitope in both dermatan sulfate and chondroitin sulfate proteoglycans of human skin. Histochem J 31:549–558. doi:10.1023/A:1003896124595
Varani J, Spearman D, Perone P et al (2001) Inhibition of type I procollagen synthesis by damaged collagen in photoaged skin and by collagenase-degraded collagen in vitro. Am J Pathol 158:931–942
Varani J, Perone P, Fligiel SE et al (2002) Inhibition of type I procollagen production in photodamage: correlation between presence of high molecular weight collagen fragments and reduced procollagen synthesis. J Invest Dermatol 119:122–129. doi:10.1046/j.1523-1747.2002.01810.x
Varani J, Schuger L, Dame MK et al (2004) Reduced fibroblast interaction with intact collagen as a mechanism for depressed collagen synthesis in photodamaged skin. J Invest Dermatol 122:1471–1479. doi:10.1111/j.0022-202X.2004.22614.x
Wight TN, Heinegard DK, Hascall VC (1991) Cell Biology of Extracellular Matrix, 2nd edn. Plenum, New York
Wight TN, Kinsella MG, Qwarnstrom EE (1992) The role of proteoglycans in cell adhesion, migration and proliferation. Curr Opin Cell Biol 4:793–801. doi:10.1016/0955-0674(92)90102-I
Wight TN, Lara S, Riessen R et al (1997) Selective deposits of versican in the extracellular matrix of restenotic lesions from human peripheral arteries. Am J Pathol 151:963–973
Wu Y, Wu J, Lee DY et al (2005) Versican protects cells from oxidative stress-induced apoptosis. Matrix Biol 24:3–13
Zako M, Shinomura T, Ujita M et al (1995) Expression of PG-M(V3), an alternatively spliced form of PG-M without a chondroitin sulfate attachment in region in mouse and human tissues. J Biol Chem 270:3914–3918. doi:10.1074/jbc.270.17.10328
Zimmermann DR, Ruoslahti E (1989) Multiple domains of the large fibroblast proteoglycan, versican. EMBO J 8:2975–2981
Zimmermann DR, Dours-Zimmermann MT, Schubert M et al (1994) Versican is expressed in the proliferating zone in the epidermis and in association with the elastic network of the dermis. J Cell Biol 124:817–825. doi:10.1083/jcb.124.5.817
Acknowledgements
The authors would like to thank G. Jopp, M. Kölln and S. Piontek for their excellent technical assistance as well as E. Knußmann-Hartig for isolation of skin biopsies.
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Knott, A., Reuschlein, K., Lucius, R. et al. Deregulation of versican and elastin binding protein in solar elastosis. Biogerontology 10, 181–190 (2009). https://doi.org/10.1007/s10522-008-9165-3
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DOI: https://doi.org/10.1007/s10522-008-9165-3