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

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

1
Amorepacific Corporation R&D Center, 314-1, Bora-dong, Giheung-gu, Yongin-si, Gyeonggi-do 446-729, Korea
2
Department of Biological Sciences, Sungkyunkwan University, 300, Cheoncheon-dong, Jangan-gu, Suwon 440-746, Korea
3
Sulloccha Research Center, Jangwon Co., Ltd., Jeju 699-924, Korea
4
School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Korea
These authors contributed equally to this paper.
*
Authors to whom correspondence should be addressed.
Received: 29 December 2013 / Revised: 4 March 2014 / Accepted: 26 March 2014 / Published: 4 April 2014
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
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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. View Full-Text
Keywords: (−)-epigallocatechin-3-O-gallate; methylated EGCG; klotho; keratinocyte differentiation (−)-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.

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