3,6-Anhydro-L-galactose increases hyaluronic acid production via the EGFR and AMPKα signaling pathway in HaCaT keratinocytes

Jae Eun Lee, Young Ah Kim, Sora Yu, So Young Park, Kyoung Heon Kim, Nam Joo Kang

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)


Background: Hyaluronic acid (HA) is an important factor in skin hydration maintenance. In mammalian keratinocytes, hyaluronan synthase 2 (HAS2) is a critical enzyme in HA production. Therefore, the promotion of HAS2 expression in keratinocytes may be a strategy for maintaining skin moisture. Objective: The aim was to determine the skin hydration effect and regulatory mechanisms of 3,6-anhydro-L-galactose (L-AHG), a main component of red macroalgal carbohydrates in human keratinocytes. Methods: L-AHG was applied to an immortalized human epidermal keratinocyte cell line (HaCaT cells). HA production, HAS2 protein and mRNA levels, and the activation of the signaling pathways involved in HAS2 expression were measured. HA levels were also evaluated for three dimensional (3D) reconstructed human skin. Results: Our results suggest that L-AHG upregulates HA production and may enhance HAS2 expression by activating EGFR-mediated ERK, PI3K/Akt, and STAT3 signaling pathways. We confirmed that L-AHG activated the AMPKα signaling pathway which in turn could regulate HAS2 expression in HaCaT cells. The effects of L-AHG on HA production were observed in the 3D reconstructed human skin model. Conclusion: Our results suggest that L-AHG may enhance skin moisture retention by increasing HA synthesis in human epidermal keratinocytes.

Original languageEnglish
Pages (from-to)90-98
Number of pages9
JournalJournal of Dermatological Science
Issue number2
Publication statusPublished - 2019 Nov

Bibliographical note

Publisher Copyright:
© 2019 The Author(s)


  • 3,6-Anhydro-L-galactose
  • Epidermal growth factor receptor
  • Hyaluronan synthase 2
  • Hyaluronic acid
  • Keratinocyte
  • Skin hydration

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology


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