The Effects of the 3-OH Group of Kaempferol on Interfollicular Epidermal Stem Cell Fate

Background: Kaempferol (3,4',5,7-tetrahydroxyflavone) is a flavonoid known to have a wide range of pharmacological activities. The 3-OH group in flavonoids has been reported to determine antioxidant activities. Objective: We tested whether kaempferol can affect the expression of integrins and the stem cell fate of interfollicular epidermal stem cells. Methods: Skin equivalent (SE) models were constructed, and the expression levels of stem cell markers and basement membrane-related antigens were tested. The immunohistochemical staining patterns of integrins, p63, and proliferating cell nuclear antigen (PCNA) were compared between kaempferol- and apigenin-treated SE models. Reverse transcription-polymerase chain reaction (RT-PCR) was used to evaluate the mRNA expression of integrins. Results: Kaempferol increased the thickness of the epidermis when added to prepare SEs. In addition, the basal cells of kaempferol-treated SEs appeared more columnar. In the immunohistological study, the expression of integrins ${\alpha}6$ and ${\beta}1$ and the numbers of p63- and PCNA-positive cells were markedly higher in the kaempferol-treated model. However, apigenin showed no effects on the formation of three-dimensional skin models. RT-PCR analysis also confirmed that kaempferol increased the expression of integrin ${\alpha}6$ and integrin ${\beta}1$. Conclusion: Our findings indicated that kaempferol can increase the proliferative potential of basal epidermal cells by modulating the basement membrane. In other words, kaempferol can affect the fate of interfollicular epidermal stem cells by increasing the expression of both integrins ${\alpha}6$ and ${\beta}1$. These effects, in particular, might be ascribed to the 3-OH group of kaempferol.