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

Author:

Bin Bum-Ho,Bhin Jinhyuk,Takaishi Mikiro,Toyoshima Koh-ei,Kawamata Saeko,Ito Kana,Hara Takafumi,Watanabe Takashi,Irié Tarou,Takagishi Teruhisa,Lee Su-Hyon,Jung Haeng-Sun,Rho Sangchul,Seo Juyeon,Choi Dong-Hwa,Hwang Daehee,Koseki Haruhiko,Ohara Osamu,Sano Shigetoshi,Tsuji Takashi,Mishima Kenji,Fukada Toshiyuki

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.

Funder

MEXT | Japan Society for the Promotion of Science

National Research Foundation

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

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