Int. J. Mol. Sci. 2014, 15(4), 5749-5761; doi:10.3390/ijms15045749
Article

Epigallocatechin-3-O-(3-O-methyl)-gallate-induced Differentiation of Human Keratinocytes Involves Klotho-Mediated Regulation of Protein Kinase-cAMP Responsive Element-Binding Protein Signaling

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Received: 29 December 2013; in revised form: 4 March 2014 / Accepted: 26 March 2014 / Published: 4 April 2014
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract: (−)-Epigallocatechin-3-O-gallate (EGCG) has long been known as a potent inducer of keratinocyte differentiation. Although its molecular mechanisms have been extensively studied, its actions on human skin remain to be elucidated. In this study, we demonstrated that methylated EGCG and EGCG increase the expression of klotho, and that klotho functions as a downstream target of EGCG and methylated EGCG in keratinocyte differentiation. We demonstrated that methylated EGCG3 and EGCG induce morphological changes in normal human epidermal keratinocytes (NHEKs) that are related to up-regulation of klotho expression. We also demonstrated that a klotho-induced keratinocyte differentiation marker in NHEKs is inhibited by H-89, a protein kinase (PKA) inhibitor. These results suggest that methylated EGCG and EGCG may function as inducers of keratinocyte differentiation via transcriptional regulation of the klotho protein.
Keywords: (−)-epigallocatechin-3-O-gallate; methylated EGCG; klotho; keratinocyte differentiation
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MDPI and ACS Style

Kim, H.-J.; Chang, H.; Han, S.H.; Lee, M.S.; Jung, J.-Y.; An, S.; Baek, S.-Y.; Lee, J.H.; Lee, J.H.; Lee, T.R.; Shin, D.W.; Kim, H. Epigallocatechin-3-O-(3-O-methyl)-gallate-induced Differentiation of Human Keratinocytes Involves Klotho-Mediated Regulation of Protein Kinase-cAMP Responsive Element-Binding Protein Signaling. Int. J. Mol. Sci. 2014, 15, 5749-5761.

AMA Style

Kim H-J, Chang H, Han SH, Lee MS, Jung J-Y, An S, Baek S-Y, Lee JH, Lee JH, Lee TR, Shin DW, Kim H. Epigallocatechin-3-O-(3-O-methyl)-gallate-induced Differentiation of Human Keratinocytes Involves Klotho-Mediated Regulation of Protein Kinase-cAMP Responsive Element-Binding Protein Signaling. International Journal of Molecular Sciences. 2014; 15(4):5749-5761.

Chicago/Turabian Style

Kim, Hyoung-June; Chang, Huikyoung; Han, Seung H.; Lee, Min S.; Jung, Ji-Yong; An, SoonAe; Baek, Seok-Yun; Lee, Jin H.; Lee, John H.; Lee, Tae R.; Shin, Dong W.; Kim, Hongtae. 2014. "Epigallocatechin-3-O-(3-O-methyl)-gallate-induced Differentiation of Human Keratinocytes Involves Klotho-Mediated Regulation of Protein Kinase-cAMP Responsive Element-Binding Protein Signaling." Int. J. Mol. Sci. 15, no. 4: 5749-5761.

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