Introduction
Zinc is a trace element found abundantly in the human skin after the skeletal muscles and bones. The skin comprises three distinct layers: the outer epidermis, the middle dermis, and the innermost layer, the subcutaneous tissue. Zinc and zinc transporters are distributed throughout the different layers of skin and have very important roles to play. Mutation or defective regulation of the zinc transporters will result in several disorders in the human body accompanied by skin manifestations. The skin manifestations of defective zinc absorption include hair loss and cutaneous rashes. Often skin manifestations should be associated with zinc deficiency or mutations and dysregulation of zinc transporters in the skin.
What Is the Form and Distribution of the Trace Element Zinc in the Human Body?
Two to three grams of zinc are present in a healthy human body. It is found most abundantly in the skeletal muscles (60 %), followed by the bones (30 percent), skin (5 percent), and liver (5 percent). In the skin, zinc is distributed through the different layers. The outermost epidermis layer contains more zinc than the other two layers. In the middle layer dermis, more zinc is found in the higher dermis than in the lower dermis. Here, zinc is present in the mast cells (innate immune cells that control the type of immune response). Since more mast cells are found in the upper dermis, it explains the presence of more zinc in the upper dermis.
In skin cells, zinc is a divalent ion (an atom that can form two covalent bonds). Tight regulation is required to maintain the state of zinc ions in the cells and is carried out by solute-linked carriers. They are:
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Zinc transporters- ZnTs (SLC30A).
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Proteins- ZIPs (SLC39A).
The ZnTs are involved in the efflux of zinc across the cells, and ZTPs are involved in zinc uptake. Apart from the zinc transporters and the proteins, metallothioneins are low molecular weight, sulphydryl-abundant proteins found in the cytoplasm. Metallothioneins will release zinc from the cytoplasm to maintain homeostasis.
What Is the Function of Zinc and Zinc Transporters in the Skin?
Zinc plays an important role as a cofactor in several enzymatic reactions in the body. It also converts DNA (deoxyribonucleic acid) to RNA (ribonucleic acid), packaging, apoptosis regulation, transcription activation, protein assembly, and lipid binding. Zinc binds to about ten percent of human proteins. Therefore, they are involved in various activities, such as cell growth, differentiation, and development.
The skin has three layers: epidermis, dermis, and subcutaneous tissue. Each skin layer consists of various cell types; they are
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Epidermis: Keratinocytes, Langerhans cells, and melanocytes.
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Dermis: Mast cells, T lymphocytes, fibroblasts, endothelial cells, and antigen-presenting cells like macrophages, dendritic cells, and monocytes.
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Subcutaneous Tissue: Subcutaneous tissue consists of adipocytes.
What Is the Role of Zinc and Zinc Transporters in Skin Cells?
Keratinocytes: Keratinocytes occupy 97 percent of the epidermis. Zinc is most abundantly distributed in the stratum spinosum layer of the epidermis. Zinc deficiency is often associated with impaired keratinolytic enzyme activities. Studies suggest that zinc is required for the proliferation of keratinocytes and suppression of inflammation in the skin. This property of zinc is used in skin ointments for ulcers and inflammation.
Langerhans Cells: Langerhans cells are associated with cutaneous manifestations of acrodermatitis enteropathica (inherited zinc deficiency caused by defective zinc absorption), which is caused by the mutation of genes coding for the ZIP (proteins involved in the regulation and homeostasis of zinc). In the skin lesions of acrodermatitis enteropathica, Langerhans cells are absent.
Melanocytes: Zinc helps in the proliferation of melanocytes in human skin. It also facilitates autophagy (self-consumption of one’s cells).
Mast Cells and Dendritic Cells: Apart from proliferative functions, zinc is an important intracellular signaling molecule. It is involved in the maturation of dendritic cells. It also promotes degranulation in the mast cells. In addition, mast cells' zinc and zinc transporters produce inflammatory cytokines.
T Cells: A zinc deficiency leads to atrophy of the thymus leading to a decrease in mature T cells. Therefore an optimal level of zinc is required in the body for T cell generation.
Endothelial Cells: Long-term zinc exposure leads to endothelial cell death, suggesting that zinc is involved in the viability of endothelial cells and angiogenesis.
Fibroblasts: Zinc is involved in glucose transport and lipogenesis in the fibroblasts and adipocytes. In addition, the zin transporters, found mainly in the connective tissues, are involved in homeostasis and proper dermis formation.
Adipocytes: Zinc inhibits the differentiation of beige fat cells. It also enhances energy consumption inhibiting obesity.
What Are the Skin Disorders Caused by Mutations in Zinc Transporters?
Mutations in the zinc transporter genes cause several genetic disorders. For example, ZIP4, ZIP13, and ZnT2 transporters mutation is associated with skin manifestations.
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Acrodermatitis Enteropathica: Mutation of ZIP4: Caused by a deficiency of zinc dues to defective absorption from the intestines. Clinically the disorder presents skin defects, hair loss, and diarrhea. The skin manifestations are referred to as acrodermatitis. They are associated with lesions on the skin of the face surrounding the mouth, anal and genital area, and acral area where there is frequent exposure to external substances.
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Spondylocheiro Dysplastic Form of Ehlers–Danlos Syndrome: Mutations in ZIP13: ZIP13 proteins are involved in connective tissue formation, and gene mutations will lead to the Spondylocheiro Dysplastic Form of Ehlers–Danlos Syndrome, characterized by hypermobility of the small joints and hyperelastic skin.
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Transient Neonatal Zinc Deficiency: Mutation in ZNT2: In healthy individuals, breast milk has a high concentration of zinc which is essential for the growth and survival of newborn babies. Mutations in the ZnT2 transporter will decrease the zinc concentration in breast milk, and the babies will show symptoms similar to acrodermatitis enteropathica.
What Are the Skin Disorders Associated With Zinc Deficiency?
Zin deficiency can occur due to defective absorption of zinc from the intestine. In addition, zinc deficiency is associated with nutritional deficiencies like pellagra (niacin) and biotin deficiency. Furthermore, skin lesions similar to acrodermatitis enteropathica and erythema are observed in nutritional deficiencies. Zinc supplements will restore the skin to normal.
Conclusion
From the above review, it is clear that zinc has a very important role in maintaining the structure and function of human skin. Deficiency is often associated with skin disorders along with several systemic manifestations. Therefore, keen attention to skin disorders should be made during examinations not to miss the possibility of zinc deficiencies.
