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Updated: Jun 17, 2026
Evaluation of Keratinocyte Proliferation on Two- and Three-dimensional Type I Collagen Substrates
Published on: April 22, 2019
Glycolic acid induces keratinocyte proliferation in a skin equivalent model via TRPV1 activation
Sumiko Denda1, Mitsuhiro Denda, Kaori Inoue
1Shiseido Research Center, 2-12-1 Fukuura, Kanazawa-ku, Yokohama 236-8643, Japan.
Background:
Glycolic acid (GA) is the most commonly used alpha-hydroxy acid (AHA) for dermatologic applications, and is considered as a versatile superficial peeling agent for facial rejuvenation. Its therapeutic effect includes acceleration of epidermal turnover without apparent inflammation, and its action is pH-dependent. However, little is known about the molecular mechanism of GA-induced peeling.
Objective:
To investigate the effects of topical application of GA on cell proliferation using a skin equivalent model and to examine the molecular mechanisms of GA-induced peeling.
Methods:
GA solution was applied on the surface of a skin equivalent model, and cell proliferation was measured by means of BrdU-incorporation and immunohistochemical methods. Release of chemical mediators such as ATP into the medium was examined. The effects of antagonists of ion channels were also analyzed.
Results:
At 24h after GA application, BrdU-incorporation into basal keratinocytes was significantly increased. Induction of keratinocyte proliferation was pH-dependent, and was inhibited by antagonists of TRPV1, an acid-sensitive ion channel. Furthermore, transient ATP release was detected in the culture medium after GA stimulation, and this was also suppressed by TRPV1 antagonists.
Conclusion:
These results suggest that one of the mechanisms of GA-induced epidermal proliferation is a growth response of basal keratinocytes to the local elevation of H(+)-ion concentration by infiltrated GA. This response is mediated by TRPV1 activation and ATP release. Activation of P2 receptors by the released ATP may also be involved.
