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.
(-)-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.
Amorepacific Corporation R&D Center, 314-1, Bora-dong, Giheung-gu, Yongin-si, Gyeonggi-do 446-729, Korea. leojune@amorepacific.com.
Hyoung-June
HJ
Kim
Amorepacific Corporation R&D Center, 314-1, Bora-dong, Giheung-gu, Yongin-si, Gyeonggi-do 446-729, Korea. jhk282@gmail.com.
Huikyoung
H
Chang
Department of Biological Sciences, Sungkyunkwan University, 300, Cheoncheon-dong, Jangan-gu, Suwon 440-746, Korea. hun2130@naver.com.
Seung Hun
SH
Han
Sulloccha Research Center, Jangwon Co., Ltd., Jeju 699-924, Korea. leems@jwgreent.co.kr.
Min Seuk
MS
Lee
Amorepacific Corporation R&D Center, 314-1, Bora-dong, Giheung-gu, Yongin-si, Gyeonggi-do 446-729, Korea. ninefog@amorepacific.com.
Ji-Yong
JY
Jung
Amorepacific Corporation R&D Center, 314-1, Bora-dong, Giheung-gu, Yongin-si, Gyeonggi-do 446-729, Korea. ananas@amorepacific.com.
SoonAe
S
An
Amorepacific Corporation R&D Center, 314-1, Bora-dong, Giheung-gu, Yongin-si, Gyeonggi-do 446-729, Korea. sybaek@amorepacific.com.
Seok-Yun
SY
Baek
Sulloccha Research Center, Jangwon Co., Ltd., Jeju 699-924, Korea. jhlee@jwgreent.co.kr.
Jin Ho
JH
Lee
Amorepacific Corporation R&D Center, 314-1, Bora-dong, Giheung-gu, Yongin-si, Gyeonggi-do 446-729, Korea. johnlee@amorepacific.com.
John Hwan
JH
Lee
Amorepacific Corporation R&D Center, 314-1, Bora-dong, Giheung-gu, Yongin-si, Gyeonggi-do 446-729, Korea. trlee@amorepacific.com.
Tae Ryong
TR
Lee
Amorepacific Corporation R&D Center, 314-1, Bora-dong, Giheung-gu, Yongin-si, Gyeonggi-do 446-729, Korea. biopang@amorepacific.com.
Dong Wook
DW
Shin
Department of Biological Sciences, Sungkyunkwan University, 300, Cheoncheon-dong, Jangan-gu, Suwon 440-746, Korea. khtcat@skku.edu.
Hongtae
H
Kim
D015415:Biomarkers; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D005707:Gallic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D005786:Gene Expression Regulation; D005966:Glucuronidase / Q000096:biosynthesis* / Q000235:genetics; D057809:HEK293 Cells; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D015603:Keratinocytes / Q000166:cytology*; D000090265:Klotho Proteins; D028321:Plant Preparations / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D034622:RNA Interference; D034741:RNA, Small Interfering; D015398:Signal Transduction; D012867:Skin / Q000187:drug effects; D013449:Sulfonamides / Q000494:pharmacology; D013662:Tea / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D015854:Up-Regulation
D015415:Biomarkers; D017362:Cyclic AMP Response Element-Binding Protein; D007546:Isoquinolines; D028321:Plant Preparations; D047428:Protein Kinase Inhibitors; D034741:RNA, Small Interfering; D013449:Sulfonamides; D013662:Tea; D005707:Gallic Acid; D005966:Glucuronidase; D000090265:Klotho Proteins; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; C573278:epigallocatechin-3-O-(3''-O-methyl)-gallate