Hyaluronan Inside and Outside of Skin

  • Aziza Wahby
  • Kathleen Daddario DiCaprio
  • Robert Stern
Chapter

Abstract

Hyaluronan is a major component of the extracellular matrix of skin and is 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 biologic processes such as cell differentiation and motility. An overview is provided here that provides recent information, bringing up-to-date advances in hyaluronan and matrix biology relevant for dermatology and skin care, with a particular emphasis on skin moisture. The differences between hyaluronan applied exogenously and that occurring naturally in the body are articulated.

References

  1. 1.
    Agren UM, Tammi M, Tammi R (1997) Hydrocortisone regulation of hyaluronan metabolism in human skin organ culture. J Cell Physiol 164(2):240–248CrossRefGoogle Scholar
  2. 2.
    Agren UM, Tammi RH, Tammi MI (1997) Reactive oxygen species contribute to epidermal hyaluronan catabolism in human skin organ culture. Free Radic Biol Med 23(7):996–1001PubMedCrossRefGoogle Scholar
  3. 3.
    Akazawa Y, Sayo T, Sugiyama Y, Sato T, Akimoto N, Ito A, Inoue S (2011) Adiponectin resides in mouse skin and upregulates hyaluronan synthesis in dermal fibroblasts. Connect Tissue Res 52(4):322–328PubMedCrossRefGoogle Scholar
  4. 4.
    Averbeck M, Gebhardt C, Anderegg U, Simon JC (2010) Suppression of hyaluronan synthase 2 expression reflects the atrophogenic potential of glucocorticoids. Exp Dermatol 19(8):757–759PubMedCrossRefGoogle Scholar
  5. 5.
    Balazs EA (1981) Hyaluronan-based composition and cosmetic formulations containing same. US Patent #4,303,676Google Scholar
  6. 6.
    Barnes L, Tran C, Sorg O, Hotz R, Grand D, Carraux P, Didierjean L, Stamenkovic I, Saurat JH, Kaya G (2010) Synergistic effect of hyaluronate fragments in retinaldehyde-induced skin hyperplasia which is a CD44-dependent phenomenon. PLoS One 5(12):e14372PubMedCrossRefGoogle Scholar
  7. 7.
    Bentley JP, Brenner RM, Linstedt AD, West NB, Carlisle KS, Rokosova BC, MacDonald N (1986) Increased hyaluronate and collagen biosynthesis and fibroblast estrogen receptors in macaque sex skin. J Invest Dermatol 87(5):668–673PubMedCrossRefGoogle Scholar
  8. 8.
    Bertheim U, Engström-Laurent A, Hofer PA, Hallgren P, Asplund J, Hellström S (2002) Loss of hyaluronan in the basement membrane zone of the skin correlates to the degree of stiff hands in diabetic patients. Acta Derm Venereol 82(5):329–334PubMedCrossRefGoogle Scholar
  9. 9.
    Botzki A, Rigden DJ, Braun S, Nukui M, Salmen S, Hoechstetter J, Bernhardt G, Dove S, Jedrzejas MJ, Buschauer A (2004) L-ascorbic acid 6-hexadecanoate, a potent hyaluronidase inhibitor. X-ray structure and molecular modeling of enzyme-inhibitor complexes. J Biol Chem 279(44):45990–45997PubMedCrossRefGoogle Scholar
  10. 10.
    Bourguignon LY, Singleton PA, Diedrich F, Stern R, Gilad E (2004) 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 279(26):26991–27007PubMedCrossRefGoogle Scholar
  11. 11.
    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 (2007) Chronic ultraviolet B irradiation causes loss of hyaluronic acid from mouse dermis because of down-regulation of hyaluronic acid synthases. Am J Pathol 171(5):1451–1461PubMedCrossRefGoogle Scholar
  12. 12.
    de la Motte C, Nigro J, Vasanji A, Rho H, Kessler S, Bandyopadhyay S, Danese S, Fiocchi C, Stern R (2009) Platelet-derived hyaluronidase 2 cleaves hyaluronan into fragments that trigger monocyte-mediated production of proinflammatory cytokines. Am J Pathol 174(6):2254–2264PubMedCrossRefGoogle Scholar
  13. 13.
    Duan J, Kasper DL (2011) Oxidative depolymerization of polysaccharides by reactive oxygen/nitrogen species. Glycobiology 21(4):401–409PubMedCrossRefGoogle Scholar
  14. 14.
    Elliott L, Rashid RM, Colome M (2010) Hyaluronic acid filler for steroid atrophy. J Cosmet Dermatol 9:253–255PubMedCrossRefGoogle Scholar
  15. 15.
    Fischer TC (2010) A European evaluation of cosmetic treatment of facial volume loss with Juvéderm™ Voluma™ in patients previously treated with Restylane SUB-Q™. J Cosmet Dermatol 9(4):291–296PubMedCrossRefGoogle Scholar
  16. 16.
    Galeano M, Polito F, Bitto A, Irrera N, Campo GM, Avenoso A, Calò M, Cascio PL, Minutoli L, Barone M, Squadrito F, Altavilla D (2011) Systemic administration of high-molecular weight hyaluronan stimulates wound healing in genetically diabetic mice. Biochim Biophys Acta 1812(7):752–759PubMedGoogle Scholar
  17. 17.
    Gasingirwa MC, Thirion J, Mertens-Strijthagen J, Wattiaux-De Coninck S, Flamion B, Wattiaux R, Jadot M (2010) Endocytosis of hyaluronidase-1 by the liver. Biochem J 430(2):305–313PubMedCrossRefGoogle Scholar
  18. 18.
    Gebhardt C, Averbeck M, Diedenhofen N, Willenberg A, Anderegg U, Sleeman JP, Simon JC (2010) Dermal hyaluronan is rapidly reduced by topical treatment with glucocorticoids. J Invest Dermatol 130(1):141–149PubMedCrossRefGoogle Scholar
  19. 19.
    Gu H, Huang L, Wong YP, Burd A (2010) HA modulation of epidermal morphogenesis in an organotypic keratinocyte-fibroblast co-culture model. Exp Dermatol 19(8):336–339CrossRefGoogle Scholar
  20. 20.
    Hargitai I, Hargittai M (2008) Molecular structure of hyaluronan: an introduction. Struct Chem 19:697–717CrossRefGoogle Scholar
  21. 21.
    Hašová M, Crhák T, Safránková B, Dvořáková J, Muthný T, Velebný V, Kubala L (2011) Hyaluronan minimizes effects of UV irradiation on human keratinocytes. Arch Dermatol Res 303(4):277–284PubMedCrossRefGoogle Scholar
  22. 22.
    Heldin P, Karousou E, Bernert B, Porsch H, Nishitsuka K, Skandalis SS (2008) Importance of hyaluronan-CD44 interactions in inflammation and tumorigenesis. Connect Tissue Res 49(3):215–218PubMedCrossRefGoogle Scholar
  23. 23.
    Huey G, Moiin A, Stern R (1990) Levels of [3H]glucosamine incorporation into hyaluronic acid by fibroblasts is modulated by culture conditions. Matrix 10(2):75–83PubMedCrossRefGoogle Scholar
  24. 24.
    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 (1999) Three isoforms of mammalian hyaluronan synthases have distinct enzymatic properties. J Biol Chem 274(35):25085–25092PubMedCrossRefGoogle Scholar
  25. 25.
    Jiang D, Liang J, Noble PW (2011) Hyaluronan as an immune regulator in human diseases. Physiol Rev 91(1):221–264PubMedCrossRefGoogle Scholar
  26. 26.
    Jokela TA, Lindgren A, Rilla K, Maytin E, Hascall VC, Tammi RH, Tammi MI (2008) Induction of hyaluronan cables and monocyte adherence in epidermal keratinocytes. Connect Tissue Res 49(3):115–119PubMedCrossRefGoogle Scholar
  27. 27.
    Kao J, Huey G, Kao R, Stern R (1990) Ascorbic acid stimulates production of glycosaminoglycans in cultured fibroblasts. Exp Mol Pathol 53(1):1–10PubMedCrossRefGoogle Scholar
  28. 28.
    Lamberg SI, Yuspa SH, Hascall VC (1986) Synthesis of hyaluronic acid is decreased and synthesis of proteoglycans is increased when cultured mouse epidermal cells differentiate. J Invest Dermatol 86(6):659–667PubMedCrossRefGoogle Scholar
  29. 29.
    Larnier C, Kerneur C, Robert L, Moczar M (1989) Effect of testicular hyaluronidase on hyaluronate synthesis by human skin fibroblasts in culture. Biochim Biophys Acta 1014(2):145–152PubMedCrossRefGoogle Scholar
  30. 30.
    Lin W, Shuster S, Maibach HI, Stern R (1997) Patterns of hyaluronan staining are modified by fixation techniques. J Histochem Cytochem 45(8):1157–1163PubMedCrossRefGoogle Scholar
  31. 31.
    Lundin A, Engström-Laurent A, Michaëlsson G, Tengblad A (1987) High levels of hyaluronate in suction blister fluid from active psoriatic lesions. Br J Dermatol 116(3):335–340PubMedCrossRefGoogle Scholar
  32. 32.
    Meyer LJ, Stern R (1994) Age-dependent changes of hyaluronan in human skin. J Invest Dermatol 102(3):385–389PubMedCrossRefGoogle Scholar
  33. 33.
    Mian N (1986) Analysis of cell-growth-phase-related variations in hyaluronate synthase activity of isolated plasma-membrane fractions of cultured human skin fibroblasts. Biochem J 237(2):333–342PubMedGoogle Scholar
  34. 34.
    Mian N (1986) Characterization of a high-Mr plasma-membrane-bound protein and assessment of its role as a constituent of hyaluronate synthase complex. Biochem J 237(2):343–357PubMedGoogle Scholar
  35. 35.
    Mio K, Stern R (2002) Inhibitors of the hyaluronidases. Matrix Biol 21(1):31–37PubMedCrossRefGoogle Scholar
  36. 36.
    Mueller BM, Schraufstatter IU, Goncharova V, Povaliy T, DiScipio R, Khaldoyanidi SK (2010) Hyaluronan inhibits postchemotherapy tumor regrowth in a colon carcinoma xenograft model. Mol Cancer Ther 9(11):3024–3032PubMedCrossRefGoogle Scholar
  37. 37.
    Nettelbladt O, Tengblad A, Hällgren R (1989) Lung accumulation of hyaluronan parallels pulmonary edema in experimental alveolitis. Am J Physiol 257(6 Pt 1):L379–L384PubMedGoogle Scholar
  38. 38.
    Oh JH, Kim YK, Jung JY, Shin JE, Chung JH (2011) Changes in glycosamino-glycans and related proteoglycans in intrinsically aged human skin in vivo. Exp Dermatol 20(5):454–456PubMedCrossRefGoogle Scholar
  39. 39.
    Oliferenko S, Paiha K, Harder T, Gerke V, Schwärzler C, Schwarz H, Beug H, Günthert U, Huber LA (1999) Analysis of CD44-containing lipid rafts: recruitment of annexin II and stabilization by the actin cytoskeleton. J Cell Biol 146(4):843–854PubMedCrossRefGoogle Scholar
  40. 40.
    Passi A, Sadeghi P, Kawamura H, Anand S, Sato N, White LE, Hascall VC, Maytin EV (2004) Hyaluronan suppresses epidermal differentiation in organotypic cultures of rat keratinocytes. Exp Cell Res 296(2):123–134PubMedCrossRefGoogle Scholar
  41. 41.
    Phillips GO, du Plessis TA, Al-Assaf S, Williams PA (2003) US Patent #6,610,810Google Scholar
  42. 42.
    Phillips GO, du Plessis TA, Al-Assaf S, Williams PA (2005) US Patent #6,841,644Google Scholar
  43. 43.
    Philipson LH, Schwartz NB (1984) Subcellular localization of hyaluronate synthetase in oligodendroglioma cells. J Biol Chem 259(8):5017–5023PubMedGoogle Scholar
  44. 44.
    Philipson LH, Westley J, Schwartz NB (1985) Effect of hyaluronidase treatment of intact cells on hyaluronate synthetase activity. Biochemistry 24(27):7899–7906PubMedCrossRefGoogle Scholar
  45. 45.
    Prusova A, Smejkolova D, Chytil M, Velebny V, Kucerik J (2010) An alternative DSC (differential scanning colorimetry) approach to study the hydration of hyaluronan. Carbohydr Polym 52(2):498–503CrossRefGoogle Scholar
  46. 46.
    Reed RK, Laurent UB, Fraser JR, Laurent TC (1990) Removal rate of [3H] hyaluronan injected subcutaneously in rabbits. Am J Physiol 259(2 Pt 2):H532–H535PubMedGoogle Scholar
  47. 47.
    Reed RK, Lilja K, Laurent TC (1988) Hyaluronan in the rat with special reference to the skin. Acta Physiol Scand 134(3):405–411PubMedCrossRefGoogle Scholar
  48. 48.
    Röck K, Fischer K, Fischer JW (2010) Hyaluronan used for intradermal injections is incorporated into the pericellular matrix and promotes proliferation in human skin fibroblasts in vitro. Dermatology 221:219–228PubMedCrossRefGoogle Scholar
  49. 49.
    Röck K, Grandoch M, Majora M, Krutmann J, Fischer JW (2011) Collagen fragments inhibit hyaluronan synthesis in skin fibroblasts in response to UVB: new insights into mechanisms of matrix remodelling. J Biol Chem 286(20):18268–18276PubMedCrossRefGoogle Scholar
  50. 50.
    Shah MG, Maibach HI (2001) Estrogen and skin. An overview. Am J Clin Dermatol 2(3):143–150PubMedCrossRefGoogle Scholar
  51. 51.
    Shearer J, Graham TE (2002) New perspectives on the storage and organization of muscle glycogen. Can J Appl Physiol 27(2):179–203PubMedCrossRefGoogle Scholar
  52. 52.
    Stair S, Carlson KW, Shuster S, Wei ET, Stern R (2002) Mystixin peptides reduce hyaluronan deposition and edema formation. Eur J Pharmacol 450(3):291–296PubMedCrossRefGoogle Scholar
  53. 53.
    Stern R, Asari AA, Sugahara KN (2006) Hyaluronan fragments: an information-rich system. Eur J Cell Biol 85(8):699–715PubMedCrossRefGoogle Scholar
  54. 54.
    Stern R, Shuster S, Wiley TS, Formby B (2001) Hyaluronidase can modulate expression of CD44. Exp Cell Res 266(1):167–176PubMedCrossRefGoogle Scholar
  55. 55.
    Stern R, Jedrzejas MJ (2006) Hyaluronidases: their genomics, structures, and mechanisms of action. Chem Rev 106(3):818–839PubMedCrossRefGoogle Scholar
  56. 56.
    Sugahara KN (2009) Hyaluronan fragments: informational polymers commandeered by cancers. In: Stern R (ed) Hyaluronan in cancer biology. Academic, San Diego, pp 221–254. ISBN 978–0–12–374178–3CrossRefGoogle Scholar
  57. 57.
    Tammi R, Säämänen AM, Maibach HI, Tammi M (1991) Degradation of newly synthesized high molecular mass hyaluronan in the epidermal and dermal compartments of human skin in organ culture. J Invest Dermatol 97(1):126–130PubMedCrossRefGoogle Scholar
  58. 58.
    Tzellos TG, Klagas I, Vahtsevanos K, Triaridis S, Printza A, Kyrgidis A, Karakiulakis G, Zouboulis CC, Papakonstantinou E (2009) Extrinsic ageing in the human skin is associated with alterations in the expression of hyaluronic acid and its metabolizing enzymes. Exp Dermatol 18(12):1028–1035PubMedCrossRefGoogle Scholar
  59. 59.
    Underhill CB (1993) Hyaluronan is inversely correlated with the expression of CD44 in the dermal condensation of the embryonic hair follicle. J Invest Dermatol 101(6):820–826PubMedCrossRefGoogle Scholar
  60. 60.
    Uzuka M, Nakajima K, Ohta S, Mori Y (1981) Induction of hyaluronic acid synthetase by estrogen in the mouse skin. Biochim Biophys Acta 673(4):387–393PubMedCrossRefGoogle Scholar
  61. 61.
    Waldenström A, Martinussen HJ, Gerdin B, Hällgren R (1991) Accumulation of hyaluronan and tissue edema in experimental myocardial infarction. J Clin Invest 88(5):1622–1628PubMedCrossRefGoogle Scholar
  62. 62.
    Weigel PH, Hascall VC, Tammi M (1997) Hyaluronan synthases. J Biol Chem 272(22):13997–14000PubMedCrossRefGoogle Scholar
  63. 63.
    Yamaguchi Y, Nagasawa T, Nakamura N, Takenaga M, Mizoguchi M, Kawai S, Mizushima Y, Igarashi R (2005) Successful treatment of photo-damaged skin of nano-scale atRA particles using a novel transdermal delivery. J Control Release 104(1):29–40PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Aziza Wahby
    • 1
  • Kathleen Daddario DiCaprio
    • 1
  • Robert Stern
    • 1
  1. 1.Department of Basic Medical SciencesTouro College of Osteopathic MedicineNew YorkUSA

Personalised recommendations