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Proc Natl Acad Sci U S A. 2017 Nov 14;114(46):12243-12248. doi: 10.1073/pnas.1710726114. Epub 2017 Oct 23.

Requirement of zinc transporter ZIP10 for epidermal development: Implication of the ZIP10-p63 axis in epithelial homeostasis.

Author information

1
Division of Pathology, Department of Oral Diagnostic Sciences, School of Dentistry, Showa University, Tokyo 142-8555, Japan; bbh82429@gmail.com fukada@ph.bunri-u.ac.jp.
2
Division of Molecular Carcinogenesis, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands.
3
Department of Dermatology, Kochi Medical School, Kochi University, Nankoku 783-8505, Japan.
4
Laboratory for Organ Regeneration, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan.
5
Molecular and Cellular Physiology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Tokushima 770-8514, Japan.
6
Laboratory for Integrative Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan.
7
Division of Pathology, Department of Oral Diagnostic Sciences, School of Dentistry, Showa University, Tokyo 142-8555, Japan.
8
Division of Anatomical and Cellular Pathology, Department of Pathology, Iwate Medical University, Iwate 028-3694, Japan.
9
Bio Solution Corporation, Seoul 139-743, Republic of Korea.
10
Institute of Environmental and Energy Technology, Pohang University of Science and Technology, Pohang 37673, Republic of Korea.
11
Amorepacific R&D Unit, Beauty in Longevity Science Research Division, Beauty Food Research Team, Youngin 17074, Republic of Korea.
12
Gyeonggi Bio Center, Gyeonggi Institute of Science and Technology Promotion, Suwon 443-270, Republic of Korea.
13
Department of New Biology, Daegu Gyeongbuk Institute of Science and Technology, Daegu 42988, Republic of Korea.
14
Laboratory for Developmental Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama 230-0042, Japan.
15
RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan.

Abstract

Skin tissues, in particular the epidermis, are severely affected by zinc deficiency. However, the zinc-mediated mechanisms that maintain the cells that form the epidermis have not been established. Here, we report that the zinc transporter ZIP10 is highly expressed in the outer root sheath of hair follicles and plays critical roles in epidermal development. We found that ZIP10 marked epidermal progenitor cell subsets and that ablating Zip10 caused significant epidermal hypoplasia accompanied by down-regulation of the transactivation of p63, a master regulator of epidermal progenitor cell proliferation and differentiation. Both ZIP10 and p63 are significantly increased during epidermal development, in which ZIP10-mediated zinc influx promotes p63 transactivation. Collectively, these results indicate that ZIP10 plays important roles in epidermal development via, at least in part, the ZIP10-zinc-p63 signaling axis, thereby highlighting the physiological significance of zinc regulation in the maintenance of skin epidermis.

KEYWORDS:

ZIP10; development; hair follicle; skin epidermis; zinc transporter

PMID:
29078349
PMCID:
PMC5699059
DOI:
10.1073/pnas.1710726114
[Indexed for MEDLINE]
Free PMC Article

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