Topical stabilized retinol treatment induces the expression of HAS genes and HA production in human skin in vitro and in vivo

Arch Dermatol Res. 2017 May;309(4):275-283. doi: 10.1007/s00403-017-1723-6. Epub 2017 Feb 28.


Skin Aging manifests primarily with wrinkles, dyspigmentations, texture changes, and loss of elasticity. During the skin aging process, there is a loss of moisture and elasticity in skin resulting in loss of firmness finally leading to skin sagging. The key molecule involved in skin moisture is hyaluronic acid (HA), which has a significant water-binding capacity. HA levels in skin decline with age resulting in decrease in skin moisture, which may contribute to loss of firmness. Clinical trials have shown that topically applied ROL effectively reduces wrinkles and helps retain youthful appearance. In the current study, ROL was shown to induce HA production and stimulates the gene expression of all three forms of hyaluronic acid synthases (HAS) in normal human epidermal keratinocytes monolayer cultures. Moreover, in human skin equivalent tissues and in human skin explants, topical treatment of tissues with a stabilized-ROL formulation significantly induced the gene expression of HAS mRNA concomitant with an increased HA production. Finally, in a vehicle-controlled human clinical study, histochemical analysis confirmed increased HA accumulation in the epidermis in ROL-treated human skin as compared to vehicle. These results show that ROL increases skin expression of HA, a significant contributing factor responsible for wrinkle formation and skin moisture, which decrease during aging. Taken together with the activity to increase collagen, elastin, and cell proliferation, these studies establish that retinol provides multi-functional activity for photodamaged skin.

Keywords: Aging; HAS3; Hyaluronic acid; Hydration; Moisture; Retinol.

MeSH terms

  • Administration, Topical
  • Aging, Premature / drug therapy*
  • Cells, Cultured
  • Elastin / metabolism
  • Gene Expression Regulation / drug effects
  • Glucuronosyltransferase / genetics
  • Glucuronosyltransferase / metabolism*
  • Humans
  • Hyaluronan Synthases
  • Hyaluronic Acid / metabolism
  • Keratinocytes / drug effects*
  • Keratinocytes / metabolism
  • Organ Culture Techniques
  • Skin / drug effects*
  • Skin / pathology
  • Skin Aging / drug effects
  • Vitamin A / therapeutic use*


  • Vitamin A
  • Hyaluronic Acid
  • Elastin
  • Glucuronosyltransferase
  • Hyaluronan Synthases