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Review
. 2018 Feb 16;10(2):219.
doi: 10.3390/nu10020219.

The Role of the Slc39a Family of Zinc Transporters in Zinc Homeostasis in Skin

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Free PMC article
Review

The Role of the Slc39a Family of Zinc Transporters in Zinc Homeostasis in Skin

Bum-Ho Bin et al. Nutrients. .
Free PMC article

Abstract

The first manifestations that appear under zinc deficiency are skin defects such as dermatitis, alopecia, acne, eczema, dry, and scaling skin. Several genetic disorders including acrodermatitis enteropathica (also known as Danbolt-Closs syndrome) and Brandt's syndrome are highly related to zinc deficiency. However, the zinc-related molecular mechanisms underlying normal skin development and homeostasis, as well as the mechanism by which disturbed zinc homeostasis causes such skin disorders, are unknown. Recent genomic approaches have revealed the physiological importance of zinc transporters in skin formation and clarified their functional impairment in cutaneous pathogenesis. In this review, we provide an overview of the relationships between zinc deficiency and skin disorders, focusing on the roles of zinc transporters in the skin. We also discuss therapeutic outlooks and advantages of controlling zinc levels via zinc transporters to prevent cutaneous disorganization.

Keywords: homeostasis; skin; transporter; zinc.

Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Zinc transporters and metallothionein (MT) are involved in intracellular zinc homeostasis. NC; nucleus, ER; endoplasmic reticulum, Zn; zinc.
Figure 2
Figure 2
ZIP4 and ZIP10 support p63 activity for adult epidermal homeostasis. ZIP4 and ZIP10 supply zinc to epidermal master regulator p63 for their activity. Zinc deficiency leads to improper function of p63, resulting in epidermal hypoplasia. Zinc is depicted as a brown circle.
Figure 3
Figure 3
ZIP10 reinforces p63 function for epidermis development. (a) ZIP10 deficiency leads to epidermal hypoplasia in mice. (b) Hematoxylin and eosin staining revealed dorsal epidermal hypoplasia and ventral embryonic epidermis (asterisk) in P1 Zip10K14 mice. C, cornified layer; G, granular layer; S, spinous layer; B, basal layer. (c) Model for ZIP10’s involvement in p63 function during epidermis development. ZIP10, whose expression is elevated from E14, contributes to the activities of increased p63 by supplying zinc. This allows p63 to properly bind to DNA for initiating gene expression for epidermis development, including cell proliferation and stratification. DC, dermal condensate; Epi, epithelium; Mes, mesenchyme; P, placode (Scale bar, 100 μm). Red (E17.5) and arrows (P2) indicate the ZIP10 protein expression. Modified from Bin et al. [36].
Figure 4
Figure 4
Ehlers–Danlos syndrome spondylodysplastic type 3 is caused by impaired collagen production due to ZIP13 dysfunction. (a) ZIP13 supplies zinc (brown circle) to SMAD proteins for their nuclear translocation. Phosphorylatoin is depicted as circled P. (b) The elder affected sib is shown at age 22 years. Patient exhibits short stature with mildly shortened trunk, antimongoloid eye slant with lack of periorbital tissue, thin and finely wrinkled skin on the palms of the hands. BMPR/TGFβR, BMP receptor/TGF-β receptor; Col, collagen. Modified from Fukada et al. [38].
Figure 5
Figure 5
ZIP7 is essential for dermis formation. (a) Five-week-old female wild-type (WT) and Zip7Col1 mice. (b) The thickness of the Azan-stained Zip7Col1 dermis is reduced. M, muscle; S, Subcutis. (c) Models for the involvement of ZIP7 in ER function. When ZIP7 is dysregulated (right), the luminal zinc level is elevated, which would induce zinc-dependent aggregation of PDIs. Therefore, protein folding and disulfide bond formation would proceed aberrantly, leading to unfolded protein responses. ER, endoplasmic reticulum; KO, knockout; PDI, protein disulfide isomerase; UPR, unfolded protein response. Modified from Bin et al. [37].

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