Hyaluronan: More than just a wrinkle filler

Glycobiology. 2016 Jun;26(6):553-9. doi: 10.1093/glycob/cww033. Epub 2016 Mar 9.


Dermatology is a field that strives not only to alleviate skin disease (therapeutics) but also to improve the perception of wellness (cosmetics). Thus, in this special issue of Glycobiology, it seems appropriate to discuss the biology of a glycosaminoglycan, called hyaluronic acid (hyaluronan, or HA), that has become the most popular agent today for intradermal injections to improve wrinkles and other cosmetic defects. HA is a simple linear polymer in which a simple disaccharide is repeated thousands of time, thereby creating a huge hydrophilic molecule that confers a large volume of hydration and contributes to the turgor and flexibility of healthy skin. Beyond cosmetic considerations, however, HA also has important biological and physiological functions that were largely under-appreciated until recently. New research has confirmed that HA is dynamically produced by most skin cells, not only fibroblasts (the cells that make most of the skin's extracellular matrix) but also by keratinocytes in the outer protective layer (epidermis). For both fibroblasts and keratinocytes, HA plays a regulatory role in controlling cell physiology through interaction of extracellular HA with a major cell-surface receptor, CD44. This interaction mediates intracellular signaling both directly and indirectly, through CD44 interactions with the cytoskeleton and with EGF and TGFβ receptors. Furthermore, degradation of HA by specific hyaluronidase enzymes produces HA fragments that can help to regulate inflammatory processes. In this review, current knowledge about the role of HA in skin inflammation and wound healing are reviewed and possible future applications of such knowledge discussed.

Keywords: fibrosis; glycosaminoglycan; inflammation; skin; wound healing.

Publication types

  • Review

MeSH terms

  • ErbB Receptors / genetics
  • ErbB Receptors / immunology
  • Extracellular Matrix / chemistry
  • Extracellular Matrix / immunology
  • Fibroblasts / chemistry
  • Fibroblasts / immunology
  • Fibroblasts / metabolism*
  • Gene Expression Regulation
  • Humans
  • Hyaluronan Receptors / genetics
  • Hyaluronan Receptors / immunology
  • Hyaluronic Acid / chemistry
  • Hyaluronic Acid / immunology
  • Hyaluronic Acid / metabolism*
  • Hyaluronic Acid / therapeutic use
  • Hyaluronoglucosaminidase / genetics
  • Hyaluronoglucosaminidase / immunology
  • Hydrophobic and Hydrophilic Interactions
  • Hypodermoclysis
  • Keratinocytes / chemistry
  • Keratinocytes / immunology
  • Keratinocytes / metabolism*
  • Receptors, Transforming Growth Factor beta / genetics
  • Receptors, Transforming Growth Factor beta / immunology
  • Signal Transduction
  • Skin / drug effects
  • Skin / injuries
  • Skin / pathology
  • Skin Aging / drug effects*
  • Skin Aging / immunology
  • Skin Aging / pathology
  • Wound Healing / drug effects*
  • Wound Healing / physiology


  • CD44 protein, human
  • Hyaluronan Receptors
  • Receptors, Transforming Growth Factor beta
  • Hyaluronic Acid
  • ErbB Receptors
  • Hyaluronoglucosaminidase