Advertisement

Hyaluronan and the Process of Aging in Skin

  • Diana Alyce Rivers
  • Robert Stern
Living reference work entry

Abstract

Hyaluronan is a major component of the extracellular matrix of skin and important in the metabolism of both epidermis and dermis. Hyaluronan is responsible for hydration, nutrient exchange, and protects against free radical damage via a multitude of signaling pathways. It is also involved in basic biological processes such as cell renewal, differentiation, and motility. An overview is provided here that provides recent information, bringing up-to-date advances in hyaluronan and matrix biology with a particular emphasis on the process of aging in human skin. The differences between hyaluronan applied exogenously and that occurring naturally in the body are articulated. A brief history is also provided of various commercial hyaluronan-containing skin-care products, including topical applications, as injectable skin fillers, and in nanoparticle delivery systems.

Keywords

Basal Lamina Dermal Fibroblast Lamellar Body Alopecia Areata Mandelic Acid 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Stern R, Maibach HI. Hyaluronan in skin: aspects of aging and its pharmacologic modulation. Clin Dermatol. 2008;26:106–22.CrossRefPubMedGoogle Scholar
  2. 2.
    Stern R. Hyaluronan: key to skin moisturization. In: Loden M, Maibach HI, editors. Dry skin and moisturizers: chemistry and function. 2nd ed. Boca Raton: CRC Press; 2005. p. 245–78.Google Scholar
  3. 3.
    Laurent TC, Fraser JR. Hyaluronan. FASEB J. 1992;6:2397–404.PubMedGoogle Scholar
  4. 4.
    Laurent TC, Laurent UB, Fraser JR. Serum hyaluronan as a disease marker. Ann Med. 1996;28:241–53.CrossRefPubMedGoogle Scholar
  5. 5.
    Laurent TC, Laurent UB, Fraser JR. The structure and function of hyaluronan: an overview. Immunol Cell Biol. 1996;74:1–7.CrossRefGoogle Scholar
  6. 6.
    Toole BP. Hyaluronan in morphogenesis. Semin Cell Dev Biol. 2001;12:79–87.CrossRefPubMedGoogle Scholar
  7. 7.
    Lee JY, Spicer AP. Hyaluronan: a multifunctional, megaDalton stealth molecule. Curr Opin Cell Biol. 2000;12:581–6.CrossRefPubMedGoogle Scholar
  8. 8.
    Aya K, Stern R. Hyaluronan in wound healing: rediscovering a major player. Wound Repair Regen. 2014;22:579–93.PubMedGoogle Scholar
  9. 9.
    Jiang D, Liang J, Noble PW. Hyaluronan as an immune regulator in human diseases. Physiol Rev. 2011;91:221–64.PubMedCentralCrossRefPubMedGoogle Scholar
  10. 10.
    Jiang D, Liang J, Noble PW. Hyaluronan in tissue injury and repair. Annu Rev Cell Dev Biol. 2007;23:435–61.CrossRefPubMedGoogle Scholar
  11. 11.
    Meyer LJ, Stern R. Age-dependent changes of hyaluronan in human skin. J Invest Dermatol. 1994;102:385–9.CrossRefPubMedGoogle Scholar
  12. 12.
    Lin W, Shuster S, Maibach HI, Stern R. Patterns of hyaluronan staining are modified by fixation techniques. J Histochem Cytochem. 1997;45:1157–63.CrossRefPubMedGoogle Scholar
  13. 13.
    Reed RK, Lilja K, Laurent TC. Hyaluronan in the rat with special reference to the skin. Acta Physiol Scand. 1988;134:405–11.CrossRefPubMedGoogle Scholar
  14. 14.
    Lamberg SI, Yuspa SH, Hascall VC. Synthesis of hyaluronic acid is decreased and synthesis of proteoglycans is increased when cultured mouse epidermal cells differentiate. J Invest Dermatol. 1986;86:659–67.CrossRefPubMedGoogle Scholar
  15. 15.
    Tammi R, Säämänen AM, Maibach HI, 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. 1991;97:126–30.CrossRefPubMedGoogle Scholar
  16. 16.
    Bourguignon LY, Singleton PA, Diedrich F, Stern R, Gilad E. CD44 interaction with Na+−H+ exchanger (NHE1) creates acidic microenvironments leading to hyaluronidase-2 and cathepsin B activation and breast tumor cell invasion. J Biol Chem. 2004;279:26991–7007.CrossRefPubMedGoogle Scholar
  17. 17.
    Oliferenko S, Paiha K, Harder T, Gerke V, Schwärzler C, Schwarz H, Beug H, Günthert U, Huber LA. Analysis of CD44-containing lipid rafts: recruitment of annexin II and stabilization by the actin cytoskeleton. J Cell Biol. 1999;146:843–54.PubMedCentralCrossRefPubMedGoogle Scholar
  18. 18.
    Jokela TA, Lindgren A, Rilla K, Maytin E, Hascall VC, Tammi RH, Tammi MI. Induction of hyaluronan cables and monocyte adherence in epidermal keratinocytes. Connect Tissue Res. 2008;49:115–9.CrossRefPubMedGoogle Scholar
  19. 19.
    Akazawa Y, Sayo T, Sugiyama Y, Sato T, Akimoto N, Ito A, Inoue S. Adiponectin resides in mouse skin and upregulates hyaluronan synthesis in dermal fibroblasts. Connect Tissue Res. 2011;52:322–8.CrossRefPubMedGoogle Scholar
  20. 20.
    Bertheim U, Engström-Laurent A, Hofer PA, Hallgren P, Asplund J, Hellström S. Loss of hyaluronan in the basement membrane zone of the skin correlates to the degree of stiff hands in diabetic patients. Acta Derm Venereol. 2002;82:329–34.CrossRefPubMedGoogle Scholar
  21. 21.
    Gu H, Huang L, Wong YP, Burd A. HA modulation of epidermal morphogenesis in an organotypic keratinocyte-fibroblast co-culture model. Exp Dermatol. 2010;19:336–9.CrossRefGoogle Scholar
  22. 22.
    Stern A, Stern R. Absence of skin rash in Goodpasture’s syndrome: the hyaluronan effect. Med Hypotheses. 2014;83:769–71.CrossRefPubMedGoogle Scholar
  23. 23.
    McBride WH, Bard JB. Hyaluronidase-sensitive halos around adherent cells. Their role in blocking lymphocyte-mediated cytolysis. J Exp Med. 1979;149:507–15.CrossRefPubMedGoogle Scholar
  24. 24.
    Delmage JM, Powars DR, Jaynes PK, Allerton SE. The selective suppression of immunogenicity by hyaluronic acid. Ann Clin Lab Sci. 1986;16:303–10.PubMedGoogle Scholar
  25. 25.
    Stern R, Asari AA, Sugahara KN. Hyaluronan fragments: an information-rich system. Eur J Cell Biol. 2006;85:699–715.CrossRefPubMedGoogle Scholar
  26. 26.
    Prusova A, Smejkolova D, Chytil M, Velebny V, Kucerik J. An alternative DSC (differential scanning colorimetry) approach to study the hydration of hyaluronan. Carbohydr Polym. 2010;52:498–503.CrossRefGoogle Scholar
  27. 27.
    Hargitai I, Hargittai M. Molecular structure of hyaluronan: an introduction. Struct Chem. 2008;19:697–717.CrossRefGoogle Scholar
  28. 28.
    Tzellos TG, Klagas I, Vahtsevanos K, Triaridis S, Printza A, Kyrgidis A, Karakiulakis G, Zouboulis CC, Papakonstantinou E. Extrinsic ageing in the human skin is associated with alterations in the expression of hyaluronic acid and its metabolizing enzymes. Exp Dermatol. 2009;18:1028–35.CrossRefPubMedGoogle Scholar
  29. 29.
    Itano N, Sawai T, Yoshida M, Lenas P, Yamada Y, Imagawa M, Shinomura T, Hamaguchi M, Yoshida Y, Ohnuki Y, Miyauchi S, Spicer AP, McDonald JA, Kimata K. Three isoforms of mammalian hyaluronan synthases have distinct enzymatic properties. J Biol Chem. 1999;274:25085–92.CrossRefPubMedGoogle Scholar
  30. 30.
    Weigel PH, Hascall VC, Tammi M. Hyaluronan synthases. J Biol Chem. 1997;272:13997–4000.CrossRefPubMedGoogle Scholar
  31. 31.
    Stern R, Jedrzejas MJ. Hyaluronidases: their genomics, structures, and mechanisms of action. Chem Rev. 2006;106:818–39.PubMedCentralCrossRefPubMedGoogle Scholar
  32. 32.
    Gasingirwa MC, Thirion J, Mertens-Strijthagen J, Wattiaux-De Coninck S, Flamion B, Wattiaux R, Jadot M. Endocytosis of hyaluronidase-1 by the liver. Biochem J. 2010;430:305–13.CrossRefPubMedGoogle Scholar
  33. 33.
    de la Motte C, Nigro J, Vasanji A, Rho H, Kessler S, Bandyopadhyay S, Danese S, Fiocchi C, Stern R. Platelet-derived hyaluronidase 2 cleaves hyaluronan into fragments that trigger monocyte-mediated production of proinflammatory cytokines. Am J Pathol. 2009;174:2254–64.PubMedCentralCrossRefPubMedGoogle Scholar
  34. 34.
    Stern R. Devising a pathway for hyaluronan catabolism. Are we there yet? Glycobiology. 2003;13:105–15.CrossRefGoogle Scholar
  35. 35.
    Shearer J, Graham TE. New perspectives on the storage and organization of muscle glycogen. Can J Appl Physiol. 2002;27:179–203.CrossRefPubMedGoogle Scholar
  36. 36.
    Mian N. Analysis of cell-growth-phase-related variations in hyaluronate synthase activity of isolated plasma-membrane fractions of cultured human skin fibroblasts. Biochem J. 1986;237:333–42.PubMedCentralCrossRefPubMedGoogle Scholar
  37. 37.
    Mian N. Characterization of a high-Mr plasma-membrane-bound protein and assessment of its role as a constituent of hyaluronate synthase complex. Biochem J. 1986;237:343–57.PubMedCentralCrossRefPubMedGoogle Scholar
  38. 38.
    Philipson LH, Schwartz NB. Subcellular localization of hyaluronate synthetase in oligodendroglioma cells. J Biol Chem. 1984;259:5017–23.PubMedGoogle Scholar
  39. 39.
    Philipson LH, Westley J, Schwartz NB. Effect of hyaluronidase treatment of intact cells on hyaluronate synthetase activity. Biochemistry. 1985;24:7899–906.CrossRefPubMedGoogle Scholar
  40. 40.
    Larnier C, Kerneur C, Robert L, Moczar M. Effect of testicular hyaluronidase on hyaluronate synthesis by human skin fibroblasts in culture. Biochim Biophys Acta. 1989;1014:145–52.CrossRefPubMedGoogle Scholar
  41. 41.
    Stern R, Shuster S, Wiley TS, Formby B. Hyaluronidase can modulate expression of CD44. Exp Cell Res. 2001;266:167–76.CrossRefPubMedGoogle Scholar
  42. 42.
    Dai G, Freudenberger T, Zipper P, Melchior A, Grether-Beck S, Rabausch B, de Groot J, Twarock S, Hanenberg H, Homey B, Krutmann J, Reifenberger J, Fischer JW. Chronic ultraviolet B irradiation causes loss of hyaluronic acid from mouse dermis because of down-regulation of hyaluronic acid synthases. Am J Pathol. 2007;171:1451–61.PubMedCentralCrossRefPubMedGoogle Scholar
  43. 43.
    Röck K, Fischer K, Fischer JW. Hyaluronan used for intradermal injections is incorporated into the pericellular matrix and promotes proliferation in human skin fibroblasts in vitro. Dermatology. 2010;221:19–28.CrossRefGoogle Scholar
  44. 44.
    Hašová M, Crhák T, Safránková B, Dvořáková J, Muthný T, Velebný V, Kubala L. Hyaluronan minimizes effects of UV irradiation on human keratinocytes. Arch Dermatol Res. 2011;303:277–84.CrossRefPubMedGoogle Scholar
  45. 45.
    Agren UM, Tammi RH, Tammi MI. Reactive oxygen species contribute to epidermal hyaluronan catabolism in human skin organ culture. Free Radic Biol Med. 1997;23:996–1001.CrossRefPubMedGoogle Scholar
  46. 46.
    Mio K, Stern R. Inhibitors of the hyaluronidases. Matrix Biol. 2002;21:31–7.CrossRefPubMedGoogle Scholar
  47. 47.
    Botzki A, Rigden DJ, Braun S, Nukui M, Salmen S, Hoechstetter J, Bernhardt G, Dove S, Jedrzejas MJ, Buschauer A. l-Ascorbic acid 6-hexadecanoate, a potent hyaluronidase inhibitor. X-ray structure and molecular modeling of enzyme-inhibitor complexes. J Biol Chem. 2004;279:45990–7.CrossRefPubMedGoogle Scholar
  48. 48.
    Volpi N, Schiller J, Stern R, Soltes L. Role, metabolism, chemical modifications and applications of hyaluronan. Curr Med Chem. 2009;16:1718–45.CrossRefPubMedGoogle Scholar
  49. 49.
    Oh JH, Kim YK, Jung JY, Shin JE, Chung JH. Changes in glycosamino-glycans and related proteoglycans in intrinsically aged human skin in vivo. Exp Dermatol. 2011;20:454–6.CrossRefPubMedGoogle Scholar
  50. 50.
    Duan J, Kasper DL. Oxidative depolymerization of polysaccharides by reactive oxygen/nitrogen species. Glycobiology. 2011;21:401–9.PubMedCentralCrossRefPubMedGoogle Scholar
  51. 51.
    Passi A, Sadeghi P, Kawamura H, Anand S, Sato N, White LE, Hascall VC, Maytin EV. Hyaluronan suppresses epidermal differentiation in organotypic cultures of rat keratinocytes. Exp Cell Res. 2004;296:123–34.CrossRefPubMedGoogle Scholar
  52. 52.
    Underhill CB. Hyaluronan is inversely correlated with the expression of CD44 in the dermal condensation of the embryonic hair follicle. J Invest Dermatol. 1993;101:820–6.CrossRefPubMedGoogle Scholar
  53. 53.
    Barnes L, Tran C, Sorg O, Hotz R, Grand D, Carraux P, Didierjean L, Stamenkovic I, Saurat JH, Kaya G. Synergistic effect of hyaluronate fragments in retinaldehyde-induced skin hyperplasia which is a CD44-dependent phenomenon. PLoS One. 2010;5:e14372.PubMedCentralCrossRefPubMedGoogle Scholar
  54. 54.
    Agren UM, Tammi M, Tammi R. Hydrocortisone regulation of hyaluronan metabolism in human skin organ culture. J Cell Physiol. 1997;164:240–8.CrossRefGoogle Scholar
  55. 55.
    Gebhardt C, Averbeck M, Diedenhofen N, Willenberg A, Anderegg U, Sleeman JP, Simon JC. Dermal hyaluronan is rapidly reduced by topical treatment with glucocorticoids. J Invest Dermatol. 2010;130:141–9.CrossRefPubMedGoogle Scholar
  56. 56.
    Averbeck M, Gebhardt C, Anderegg U, Simon JC. Suppression of hyaluronan synthase 2 expression reflects the atrophogenic potential of glucocorticoids. Exp Dermatol. 2010;19:757–9.CrossRefPubMedGoogle Scholar
  57. 57.
    Shah MG, Maibach HI. Estrogen and skin. An overview. Am J Clin Dermatol. 2001;2:143–50.CrossRefPubMedGoogle Scholar
  58. 58.
    Bentley JP, Brenner RM, Linstedt AD, West NB, Carlisle KS, Rokosova BC, MacDonald N. Increased hyaluronate and collagen biosynthesis and fibroblast estrogen receptors in macaque sex skin. J Invest Dermatol. 1986;87:668–73.CrossRefPubMedGoogle Scholar
  59. 59.
    Uzuka M, Nakajima K, Ohta S, Mori Y. Induction of hyaluronic acid synthetase by estrogen in the mouse skin. Biochim Biophys Acta. 1981;673:387–93.CrossRefPubMedGoogle Scholar
  60. 60.
    Huey G, Moiin A, Stern R. Levels of [3H]glucosamine incorporation into hyaluronic acid by fibroblasts is modulated by culture conditions. Matrix. 1990;10:75–83.CrossRefPubMedGoogle Scholar
  61. 61.
    Kao J, Huey G, Kao R, Stern R. Ascorbic acid stimulates production of glycosaminoglycans in cultured fibroblasts. Exp Mol Pathol. 1990;53:1–10.CrossRefPubMedGoogle Scholar
  62. 62.
    Ditre CM, Griffin TD, Murphy GF, Sueki H, Telegan B, Johnson WC, Yu RJ, Van Scott EJ. Effects of alpha-hydroxy acids on photoaged skin: a pilot clinical, histologic, and ultrastructural study. J Am Acad Dermatol. 1996;34:187–95.CrossRefPubMedGoogle Scholar
  63. 63.
    Fischer TC. A European evaluation of cosmetic treatment of facial voume loss with JuvédermTM VolumaTM in patients previously treated with Restylane SUB-QTM. J Cosmet Dermatol. 2010;9:291–6.CrossRefPubMedGoogle Scholar
  64. 64.
    Elliott L, Rashid RM, Colome M. Hyaluronic acid filler for steroid atrophy. J Cosmet Dermatol. 2010;9:253–5.CrossRefPubMedGoogle Scholar
  65. 65.
    Balazs EA. Hyaluronan-based composition and cosmetic formulations containing same. US Patent #4,303,676. 1981.Google Scholar
  66. 66.
    Phillips GO, du Plessis TA, Al-Assaf S, Williams PA. US Patent #6,610,810. 2003.Google Scholar
  67. 67.
    Phillips GO, du Plessis TA, Al-Assaf S, Williams PA. US Patent #6,841,644. 2005.Google Scholar
  68. 68.
    Yamaguchi Y, Nagasawa T, Nakamura N, Takenaga M, Mizoguchi M, Kawai S, Mizushima Y, Igarashi R. Successful treatment of photo-damaged skin of nano-scale atRA particles using a novel transdermal delivery. J Control Release. 2005;104:29–40.CrossRefPubMedGoogle Scholar
  69. 69.
    Gupta S, Bansal R, Gupta S, Jindal N, Jindal A. Nanocarriers and nanoparticles for skin care and dermatological treatments. Indian Dermatol Online J. 2013;4:267–72.PubMedCentralCrossRefPubMedGoogle Scholar
  70. 70.
    Röck K, Grandoch M, Majora M, Krutmann J, Fischer JW. Collagen fragments inhibit hyaluronan synthesis in skin fibroblasts in response to UVB: new insights into mechanisms of matrix remodeling. J Biol Chem. 2011;286:18268–76.PubMedCentralCrossRefPubMedGoogle Scholar
  71. 71.
    Galeano M, Polito F, Bitto A, Irrera N, Campo GM, Avenoso A, Calò M, Cascio PL, Minutoli L, Barone M, Squadrito F, Altavilla D. Systemic administration of high-molecular weight hyaluronan stimulates wound healing in genetically diabetic mice. Biochim Biophys Acta. 2011;1812:752759.Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  1. 1.The Department of Basic Biomedical SciencesTouro College of Osteopathic MedicineNew YorkUSA

Personalised recommendations