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

Kim HJ, Chang H, Han SH, Lee MS, Jung JY, An S, Baek SY, Lee JH, Lee JH, Lee TR, Shin DW, Kim H
Source: Int J Mol Sci
Publication Date: (2014)
Issue: 15(4): 5749-61
Research Area:
Basic Research
Cells used in publication:
Keratinocyte, (NHEK-Ad) human adult
Species: human
Tissue Origin: dermal
Keratinocyte, (NHEK-neo) human neonatal
Species: human
Tissue Origin: dermal


(-)-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.