title: ZIP2 protein, a zinc transporter, is associated with keratinocyte differentiation.
abstract: Zinc is essential for the proper functioning of various enzymes and transcription factors, and its homeostasis is rigorously controlled by zinc transporters (SLC39/ZIP, importers; SLC30/ZnT, exporters). Skin disease is commonly caused by a zinc deficiency. Dietary and inherited zinc deficiencies are known to cause alopecia and the development of vesicular or pustular dermatitis. A previous study demonstrated that zinc played crucial roles in the survival of keratinocytes and their unique functions. High levels of zinc have been detected in the epidermis. Epidermal layers are considered to use a mechanism that preferentially takes in zinc, which is involved with the unique functions of keratinocytes. However, few studies have investigated the ZIP (Zrt- and Irt-like protein) proteins specifically expressed in keratinocytes and their functions. We explored the ZIP proteins specifically expressed in the epidermis and analyzed their functions. Gene expression analysis showed that the expression of ZIP2 was consistently higher in the epidermis than in the dermis. Immunohistochemistry analysis confirmed the expression of ZIP2 in differentiating keratinocytes. The expression of ZIP2 was found to be up-regulated by the differentiation induction of cultured keratinocytes. Intracellular zinc levels were decreased in keratinocytes when ZIP2 was knocked down by siRNA, and this subsequently inhibited the differentiation of keratinocytes. Moreover, we demonstrated that ZIP2 knockdown inhibited the normal formation of a three-dimensional cultured epidermis. Taken together, the results of this study suggest that ZIP2, a zinc transporter expressed specifically in the epidermis, and zinc taken up by ZIP2 are necessary for the differentiation of keratinocytes.
authors.affiliation: From the Research Laboratories, Nippon Menard Cosmetic Co., Ltd., 2-7 Torimicho, Nishi-Ku, Nagoya, Aichi 451-0071, Japan, the Department of Cellular Biophysics, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1, Tanabedori, Mizuho-Ku, Nagoya, Aichi 467-8603, Japan, inoue.yuu@menard.co.jp.
authors.forename: Yu
authors.initials: Y
authors.lastname: Inoue
authors.affiliation: From the Research Laboratories, Nippon Menard Cosmetic Co., Ltd., 2-7 Torimicho, Nishi-Ku, Nagoya, Aichi 451-0071, Japan, the Departments of Dermatology and the Menard Collaborative Research Chair, Nagoya University Graduate School of Medicine, 65 Tsurumaicho, Showa-Ku, Nagoya, Aichi 466-8560, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Hasegawa
authors.affiliation: From the Research Laboratories, Nippon Menard Cosmetic Co., Ltd., 2-7 Torimicho, Nishi-Ku, Nagoya, Aichi 451-0071, Japan.
authors.forename: Sadanori
authors.initials: S
authors.lastname: Ban
authors.affiliation: From the Research Laboratories, Nippon Menard Cosmetic Co., Ltd., 2-7 Torimicho, Nishi-Ku, Nagoya, Aichi 451-0071, Japan, the Departments of Dermatology and Applied Cell and Regenerative Medicine, Fujita Health University School of Medicine, 1-98 Kutsukakecho, Toyoake, Nagoya, Aichi 470-1192, Japan, and.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Yamada
authors.affiliation: From the Research Laboratories, Nippon Menard Cosmetic Co., Ltd., 2-7 Torimicho, Nishi-Ku, Nagoya, Aichi 451-0071, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Date
authors.affiliation: From the Research Laboratories, Nippon Menard Cosmetic Co., Ltd., 2-7 Torimicho, Nishi-Ku, Nagoya, Aichi 451-0071, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mizutani
authors.affiliation: From the Research Laboratories, Nippon Menard Cosmetic Co., Ltd., 2-7 Torimicho, Nishi-Ku, Nagoya, Aichi 451-0071, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Nakata
authors.affiliation: the Department of Cellular Biophysics, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1, Tanabedori, Mizuho-Ku, Nagoya, Aichi 467-8603, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Tanaka
authors.affiliation: the Department of Cellular Biophysics, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1, Tanabedori, Mizuho-Ku, Nagoya, Aichi 467-8603, Japan.
authors.forename: Naohide
authors.initials: N
authors.lastname: Hirashima
mesh_terms: D000818:Animals; D001483:Base Sequence; D027682:Cation Transport Proteins / Q000235:genetics / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D017931:DNA Primers; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006801:Humans; D015603:Keratinocytes / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D027682:Cation Transport Proteins; D017931:DNA Primers; D034741:RNA, Small Interfering; C498424:SLC39A2 protein, human; C498425:Slc39a2 protein, mouse
keywords: Cell Differentiation; Epidermis; Keratinocyte; Transporter; Zinc