Abstract
Skin aging is characterised by a progressive deterioration of its functional properties, linked to alterations of dermal connective tissue. Whereas many studies have been devoted to collagen alterations during aging, the situation is less clear concerning glycosaminoglycans and proteoglycans. Particularly, the alterations of the expression of small leucine-rich proteoglycans (SLRPs), a family of proteoglycans strongly implicated in cell regulation, have never been studied.
In the present study we measured glycosaminoglycans and small leucine-rich proteoglycans synthesis by skin fibroblasts from donors of 1 month to 83 years old. [3H]-glucosamine and [35S]-sulfate incorporation did not show significant differences of sulfated GAG synthesis during aging. On the other hand, a significant positive correlation was found between hyaluronan secretion and donor’s age. Northern blot analysis of SLRPs mRNAs showed a significant negative correlation of lumican mRNA with donor’s age, whereas decorin and biglycan mRNAs were not significantly altered. Immunohistochemical study and quantitative image analysis confirmed a decreased lumican accumulation in aged human skin.
Taken together, our results suggest that impairment of glycosaminoglycans and SLRPs synthesis might be involved in the functional alterations of aged skin.
Similar content being viewed by others
Abbreviations
- SLRPs:
-
Small Leucine-Rich Proteoglycans
- GAGs:
-
glycosaminoglycans
References
Iozzo RV: Matrix proteoglycans from molecular design to cellular function. Annu Rev Biochem 67: 609–652, 1998
Zimmerman DR: Versican. In : RV Iozzo (ed). Proteoglycans: structure, biology and molecular interactions. Marcel Dekker, New York, Basel, 2000, pp 327–341
Bianco P, Fisher LW, Young MF, Termine DJ, Robey PG: Expression and localization of the two small proteoglycans biglycan and decorin in developing human skeletal and non skeletal tissues. J Histochem Cytochem 38: 1549–1563, 1990
Ying S, Shiraishi A, Kao CW, et al.: Characterization and expression of the mouse lumican gene. J Biol Chem 272: 30306–30313, 1997
Neame PJ, Kay CJ: Small Leucine-Rich Proteoglycans. In: RV Iozzo (ed). Proteoglycans : Structure, biology and molecular interactions. Marcel Dekker, New York, Basel, 2000, pp 201–235
Carrino DA, Onnerfjord P, Sandy JD, et al.: Age-related changes in the proteoglycans of human skin. Specific cleavage of decorin to yield a major catabolic fragment in adults skin. J Biol Chem 278: 17566–17572, 2003
Danielson KG, Barribault H, Gomes DF, Graham H, Kadler KE, Iozzo RV: Targeted disruption of decorin leads to abnormal collagen fibril morphology and skin fragility. J Cell Biol 136: 729–753, 1997
Wegrowski Y, Gillery P, Kotlarz G, Perreau C, Georges N, Maquart FX: Modulation of sulfated glycosaminoglycan and small proteoglycan synthesis by the extracellular matrix. Mol Cell Biochem 205: 125–131, 2000
Grover J, Chen XN, Korenberg JR, Roughley PJ: The human lumican gene. Organization, chromosomal location, and expression in articular cartilage. J Biol Chem: 270, 21942–21949, 1995
Chakravarti S, Magnuson T, Lass JH, Jepsen KJ, La Mantia C, Carrol H: Lumican regulates collagen fibril assembly: skin fragility and corneal opacity in the absence of lumican. J Cell Biol 141: 1227–1286, 1998
Ameye L, Young MF: Mice deficient in small leucine-rich proteoglycans: novel in vivo models for osteoporosis, osteoarthritis, Ehlers-Danlos syndrome, muscular dystrophy, and corneal diseases. Glycobiology 12: 107R–116R, 2002
De Luca A, Santra M, Baldi A, Giordano A, Iozzo RV: Decorin-induced growth suppression is associated with up-regulation of p21, an inhibitor of cyclin-dependent kinase. J Biol Chem 271: 18961–18965, 1996
Yamaguchi Y, Mann DM, Ruoslahti E: Negative regulation of transforming growth factor-β by the proteoglycan decorin. Nature 346: 821–824, 1990
Santra M, Mann DM, Mercer EW, Skorski T, Calabretta B, Iozzo RV: Ectopic expression of decorin protein core causes a generalized growth suppression in neoplastic cells of various histogenetic origin and requires endogenous p21, an inhibitor of cyclin-dependent kinases. J Clin Invest 100: 149–157, 1997
Kinsella MG, Tsoi CK, Jarvelaïnen HT, Wight TN: Selective expression and processing of biglycan during migration of bovine aortic endothelial cells. The role of endogenous basic fibroblasts growth factor. J Biol Chem 272: 318–325,1997
Weber CK, Sommer G, Michl P, et al.: Biglycan is overexpressed in pancreatic cancer and induces G1 arrest in pancreatic cancer cell lines. Gastroenterology 121: 657–667, 2001
Bradford MM: A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72: 248–254, 1976
Wasteson A, Uthne K, Westermark B: A novel assay for the biosynthesis of sulphated polysaccharide and its application to studies on the effects of somatomedin on cultured cells. Biochem J 136: 1069–1074, 1973
Glimelius B, Pintar JE: Analysis of developmentally homogeneous neural crest cell populations in vitro. IV. Cell proliferation and synthesis of glycosaminoglycans. Cell Differ 10: 173–182, 1981
Wessler E: Electrophoresis of acidic glycosaminoglycans in hydrochloric acid: a micro method for sulfate determination. Anal Biochem 41: 67–69, 1971
Bartold PM, Wiebkin OW, Thonard JC: Molecular weight estimation of sulfated glycosaminoglycans in human gingivae. Connect Tissue Res 9: 165–172, 1982
Wegrowski Y: Effect of hyperthermia on the extracellular matrix. I. Heat enhances hyaluronan and inhibits sulphated glycosaminoglycan synthesis. FEBS Lett 334: 121–124, 199
Saito H, Yamagata T, Suzuki S: Enzymatic methods for the determination of small quantities of isomeric chondroitin sulfates. J Biol Chem 243: 1536–1542, 1986
Chomczynski P, Sacchi N: Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction.Anal Biochem. 162: 156–159, 1987
Sambrook J, Fritsch E, Maniatis T: Molecular Cloning: A Laboratory Manual, 2nd edn. Cold Spring Harbor Laboratory, 1989
Fisher LW, Stubbs JT 3rd, Young MF: Antisera and cDNA probes to human and certain animal model bone matrix noncollagenous proteins. Acta Orthop Scand Suppl 266: 61–65, 1995
Masiakowski P, Breathnach R, Bloch J, Gannon F, Krust A, Chambon P: Cloning of cDNA sequences of hormone-regulated genes from the MCF-7 human breast cancer cell line. Nucl Ac Res 10: 7895–7903, 1982
Brown JA. The effects of ageing on fibroblast function during proliferation. J Wound Care. 13: 94–96, 2004
Chen QM. Replicative senescence and oxidant-induced premature senescence. Beyond the control of cell cycle checkpoints. Ann N Y Acad Sci. 908: 111–125, 2000
Campisi J: The role of cellular senescence in skin aging. J Invest Dermatol Symp Proc. 3: 1–5, 1998
Xu T, Bianco P, Fisher L, Longenecker G, et al.: Targeted disruption of the biglycan gene leads to an osteoporosis-like phenotype in mice. Nature Genet 20: 78–82, 1998
Pogany G, Hernandez DJ, Vogel KG: The in vitro interaction of proteoglycans with type I collagen is modulated by phosphate. Arch Biochem Biophys 313: 102–111, 1994
Pins GD, Christiansen DL, Patel R, Silver FH: Self-assembly of collagen fibers. Influence of fibrillar alignment and decorin on mechanical properties. Biophys J 73: 2164–2172, 1997
Breen M, Weinstein HG, Johnson BL, Veis A, Marshall RT: Acidic glycosaminoglycans in human skin during fetal development and adult life. Biochim Biophys Acta 201: 54–60, 1970
Fleischmajer R, Perlish J, Bashey RI: Human dermal glycosaminoglycans and aging. Biochim Biophys Acta 279: 265–275, 1972
Meyer LJM, Stern R: Age-dependent changes of hyaluronan in human skin. J Invest Dermatol 102: 385–389, 1994
Carrino DA, Sorrell JM, Caplan AI: Age-related changes in the proteoglycans of human skin. Arch Biochem Biophys 373: 91–101, 2000
Takeda K, Gosiewska A, Peterkofsky B: Similar, but not identical, modulation of expression of extracellular matrix components during in vitro and in vivo aging of human skin fibroblasts. J Cell Physiol 153: 450–459, 1992
Passi A, Albertini R, Campagnari F, De Luca G: Modifications of proteoglycans secreted into the growth medium by young and senescent human skin fibroblasts. FEBS Lett. 402: 286–290, 1997
Davidson EA, Small W: Metabolism in vivo of connective tissue mucopolysaccharides II. Chondroitin sulfate and hyaluronic acid of skin. Biochim Biophys Acta 69: 53–458, 1963
Fodil-Bourahla I, Drubaix I, Robert L: Effect of in vitro aging on the biosynthesis of glycosaminoglycans by human skin fibroblasts. Modulation by the elastin-laminin receptor. Mech Ageing Dev 106: 241–260, 1999
Tammi R, Säämänen AM, Maibach ME, Tammi M: Degradation of newly synthesized high molecular mass hyaluronan in the epidermal and dermal compartments of human skin in organ culture. J Invest Dermatol 97: 126–130, 1991
Willen MD, Sorrell JM, Lekan CC, Davis BT, Caplan AI: Patterns of glycosaminoglycan/proteoglycan immunostaining in human skin during aging. J Invest Dermatol 96: 968–974, 1991
Nomura Y, Abe Y, Ishii Y, Watanabe M, Kobayashi M, Hattori A, Tsujimoto M: Structural changes in the glycosaminoglycan chain of rat skin decorin with growth. J Dermatol 30: 655–664, 2003
Bernstein EF, Fisher LW, Li K, Le Baron RG, Tan EML, Uitto J: Differential expression of the versican and decorin genes in photoaged and sun-protected skin. Lab Invest 72: 662–669, 1995
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Vuillermoz, B., Wegrowski, Y., Contet-Audonneau, JL. et al. Influence of aging on glycosaminoglycans and small leucine-rich proteoglycans production by skin fibroblasts. Mol Cell Biochem 277, 63–72 (2005). https://doi.org/10.1007/s11010-005-5073-x
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/s11010-005-5073-x