title: Upregulation of aquaporin-3 is involved in keratinocyte proliferation and epidermal hyperplasia.
abstract: Aquaporin-3 (AQP3) is a water/glycerol-transporting protein expressed in keratinocytes of the epidermis. We previously showed that AQP3-mediated transport of water and glycerol is involved in keratinocyte migration and proliferation, respectively. However, the involvement of AQP3 in epidermal hyperplasia in skin diseases, such as atopic dermatitis (AD), is unknown. In this study, we found significantly increased AQP3 transcript and protein expression in the epidermis of human AD lesions. The upregulation of AQP3 expression in human keratinocytes by transfection with human AQP3 DNA plasmid was associated with increased cellular glycerol and ATP, as well as increased cell proliferation. Among several cytokines and chemokines produced in the skin, CCL17, which is highly expressed in AD, was found to be a strong inducer of AQP3 expression and enhanced keratinocyte proliferation. In mouse AD models, AQP3 was strongly overexpressed in the epidermis in wild-type mice. Epidermal hyperplasia was reduced in AQP3-deficient mice, with a decreased number of proliferating keratinocytes. These results suggest the involvement of AQP3 in epidermal hyperplasia by a mechanism involving upregulated AQP3 expression and consequent enhancement of keratinocyte proliferation.
authors.affiliation: Department of Dermatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Nakahigashi
authors.forename: Kenji
authors.initials: K
authors.lastname: Kabashima
authors.forename: Akihiko
authors.initials: A
authors.lastname: Ikoma
authors.forename: Alan S
authors.initials: AS
authors.lastname: Verkman
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Miyachi
authors.forename: Mariko
authors.initials: M
authors.lastname: Hara-Chikuma
mesh_terms: D000818:Animals; D051400:Aquaporin 3 / Q000235:genetics / Q000378:metabolism*; D002455:Cell Division / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D003876:Dermatitis, Atopic / Q000378:metabolism* / Q000473:pathology*; D004195:Disease Models, Animal; D004817:Epidermis / Q000473:pathology; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D006965:Hyperplasia; D015603:Keratinocytes / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D008812:Mice, Hairless; D008817:Mice, Mutant Strains; D015854:Up-Regulation / Q000502:physiology
chemical_list: C496027:AQP3 protein, human; C496028:Aqp3 protein, mouse; D051400:Aquaporin 3