Cited by 94Trace Elements in HealthHair Growth and DisordersPlant Micronutrient Interactions and Effects

ZIP2 protein, a zinc transporter, is associated with keratinocyte differentiation

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Inoue, Yu, Hasegawa, Seiji, Ban, Sadanori, Yamada, Takaaki, Date, Yasushi, Mizutani, Hiroshi, Nakata, Satoru, Tanaka, Masahiko +1 more·2014·Journal of Biological Chemistry

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.

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Crossref · 10.1074/jbc.m114.560821

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  • The ZIP2 protein, a zinc transporter, is essential for the differentiation of keratinocytes.

    “The ZIP2 protein, a zinc transporter, is essential for the differentiation of keratinocytes [103].”

    From Bioactive Compounds for Skin Health: A Review (2021) · cites this paper as [103]

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Authors
Inoue, Y., Hasegawa, S., Ban, S., Yamada, T., Date, Y., Mizutani, H., Nakata, S., Tanaka, M., & Hirashima, N.
Affiliations
  • Nagoya City University (JP)
  • Fujita Health University (JP)
  • Nippon Menard Cosmetic (Japan) (JP)
Corresponding author
Inoue, Yu
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2014-08
Volume
289
Issue
31
Pages
21451-21462
ISSN
0021-9258 (ISSN-L)
OpenAlex
W2081337005
Cited by
87
References
28
Citations by year
2026: 4 · 2025: 5 · 2024: 11 · 2023: 6 · 2022: 7 · 2021: 9 · 2020: 8 · 2019: 7 · 2018: 12 · 2017: 10 · 2016: 2 · 2015: 6
FWCI
5.59
Type
journal article
Language
en
Open access
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
Japan Society for the Promotion of Science (25430040)
Topics
  • Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
  • Health Sciences › Medicine › Urology › Hair Growth and Disorders
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Plant Micronutrient Interactions and Effects
Keywords
ZIP2, zinc transporters, keratinocyte differentiation, zinc homeostasis, epidermis, zinc deficiency, hair loss, pustular dermatitis, epidermal differentiation, siRNA knockdown
MeSH terms
Epidermal Cells, Animals, Base Sequence, Cell Differentiation, Cells, Cultured, Epidermis, Humans, Keratinocytes, DNA Primers, Cation Transport Proteins, RNA, Small Interfering, Mice, Gene Knockdown Techniques, Real-Time Polymerase Chain Reaction

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