title: 24-hour rhythm of aquaporin-3 function in the epidermis is regulated by molecular clocks.
abstract: Aquaporin 3 (AQP3) is located in the basal layer of the epidermis and regulates biological functions of skin such as water content and trans-epidermal water loss. A recent study showed that the biological function of skin exhibits a 24-hour rhythm, but the molecular mechanism of the variation remains poorly understood. Here we show that mice mutated in the core clock component CLOCK (Clk/Clk) show decreased stratum corneum hydration. An extensive search for the underlying cause led us to identify AQP3 as a new regulator to control the 24-hour variation in biological functions of skin. In mouse epidermis of wild-type mice, mAqp3 exhibits circadian rhythms; however, these are significantly decreased in Clk/Clk. Luciferase reporter gene analysis revealed that transcription of mAqp3 is activated by D-site-binding protein, a clock gene. A human homolog, hAQP3, also exhibited significant oscillation in human keratinocyte (HaCaT) cells synchronized with medium containing 50% serum, and this rhythm was regulated by the endogenous CLOCK/BMAL1 heterodimer. These data indicate that although the molecular mechanisms underlying the rhythmic expression of mAqp3 and hAQP3 are different, clock genes are involved in time-dependent skin hydration. Our current findings provide a molecular link between the circadian clock and AQP3 function in mouse dorsal skin and HaCaT cells.
authors.affiliation: Faculty of Pharmaceutical Sciences, Division of Clinical Pharmacy, Department of Pharmaceutics, Department of Medico-Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Matsunaga
authors.affiliation: Faculty of Pharmaceutical Sciences, Division of Clinical Pharmacy, Department of Pharmaceutics, Department of Medico-Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Kazufumi
authors.initials: K
authors.lastname: Itcho
authors.affiliation: Faculty of Pharmaceutical Sciences, Division of Clinical Pharmacy, Department of Pharmaceutics, Department of Medico-Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan; Research Fellow of Japan Society for the Promotion of Science, Tokyo, Japan.
authors.forename: Kengo
authors.initials: K
authors.lastname: Hamamura
authors.affiliation: Faculty of Pharmaceutical Sciences, Division of Clinical Pharmacy, Department of Pharmaceutics, Department of Medico-Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Eriko
authors.initials: E
authors.lastname: Ikeda
authors.affiliation: Faculty of Pharmaceutical Sciences, Division of Clinical Pharmacy, Department of Pharmaceutics, Department of Medico-Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Hisako
authors.initials: H
authors.lastname: Ikeyama
authors.affiliation: Faculty of Pharmaceutical Sciences, Division of Clinical Pharmacy, Department of Pharmaceutics, Department of Medico-Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Furuichi
authors.affiliation: Faculty of Pharmaceutical Sciences, Division of Clinical Pharmacy, Department of Pharmaceutics, Department of Medico-Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Miyako
authors.initials: M
authors.lastname: Watanabe
authors.affiliation: Faculty of Pharmaceutical Sciences, Division of Clinical Pharmacy, Department of Pharmaceutics, Department of Medico-Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Koyanagi
authors.affiliation: Faculty of Pharmaceutical Sciences, Division of Clinical Pharmacy, Department of Pharmaceutics, Department of Medico-Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan. Electronic address: ohdo@phar.kyushu-u.ac.jp.
authors.forename: Shigehiro
authors.initials: S
authors.lastname: Ohdo
mesh_terms: D000818:Animals; D051400:Aquaporin 3 / Q000378:metabolism*; D056926:CLOCK Proteins / Q000378:metabolism; D002460:Cell Line; D057906:Circadian Clocks; D002940:Circadian Rhythm; D004817:Epidermis / Q000378:metabolism* / Q000502:physiology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006801:Humans; D015603:Keratinocytes / Q000166:cytology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009154:Mutation; D011401:Promoter Regions, Genetic; D055503:Protein Multimerization; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D014158:Transcription, Genetic; D014867:Water / Q000502:physiology
chemical_list: C496027:AQP3 protein, human; C496028:Aqp3 protein, mouse; D012333:RNA, Messenger; D014867:Water; D051400:Aquaporin 3; D056926:CLOCK Proteins