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.
MeSH terms
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Biomarkers
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Cell Differentiation / drug effects*
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Cell Line
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Cell Survival
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Cyclic AMP Response Element-Binding Protein / metabolism*
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Gallic Acid / analogs & derivatives*
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Gallic Acid / pharmacology
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Gene Expression Regulation
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Glucuronidase / biosynthesis*
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Glucuronidase / genetics
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HEK293 Cells
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Histamine Release / drug effects
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Humans
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Isoquinolines / pharmacology
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Keratinocytes / cytology*
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Klotho Proteins
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Plant Preparations / pharmacology
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Protein Kinase Inhibitors / pharmacology
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RNA Interference
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RNA, Small Interfering
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Signal Transduction
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Skin / drug effects
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Sulfonamides / pharmacology
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Tea / metabolism
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Transcription, Genetic / drug effects
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Up-Regulation
Substances
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Biomarkers
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Cyclic AMP Response Element-Binding Protein
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Isoquinolines
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Plant Preparations
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Protein Kinase Inhibitors
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RNA, Small Interfering
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Sulfonamides
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Tea
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Gallic Acid
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Glucuronidase
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Klotho Proteins
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N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide
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epigallocatechin-3-O-(3''-O-methyl)-gallate