An Acrodermatitis Enteropathica-Associated Zn Transporter, ZIP4, Regulates Human Epidermal Homeostasis
| Autor: | Jinhyuk Bhin, Dae-Kyum Kim, Daehee Hwang, Eun-Gyung Cho, Juyeon Seo, Bum-Ho Bin, Su-Hyon Lee, Toshiyuki Fukada, Haeng-Sun Jung, Tae Ryong Lee, Ai-Young Lee, Nan-Hyung Kim |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Adult
Keratinocytes Male 0301 basic medicine medicine.medical_specialty Blotting Western Human skin Dermatology Biology Real-Time Polymerase Chain Reaction Biochemistry Sampling Studies Pathogenesis Young Adult 03 medical and health sciences Reference Values Internal medicine medicine Homeostasis Humans Metallothionein RNA Small Interfering Cation Transport Proteins Molecular Biology Gene Cells Cultured Aged Gene knockdown integumentary system Acrodermatitis Acrodermatitis enteropathica Cell Differentiation Cell Biology Middle Aged medicine.disease Cell biology Blot Zinc 030104 developmental biology Endocrinology Gene Expression Regulation Female Epidermis Carrier Proteins |
| Zdroj: | Journal of Investigative Dermatology. 137:874-883 |
| ISSN: | 0022-202X |
| DOI: | 10.1016/j.jid.2016.11.028 |
| Popis: | Acrodermatitis enteropathica is an autosomal recessive disorder characterized by scaly eczematous dermatosis accompanied by alopecia and diarrhea. Various mutations in the SLC39A4 gene (ZIP4), which encodes a zinc transporter, are responsible for this disorder. However, the molecular mechanism underlying the involvement of ZIP4 in the pathogenesis of this condition has yet to be established. In this study, we report the role of ZIP4 in human epidermis. ZIP4 is predominantly expressed in human keratinocytes, and its expression is dramatically reduced on epidermal differentiation. ZIP4 knockdown in human keratinocytes down-regulates zinc (Zn) levels and the transcriptional activity of a key epidermal Zn-binding protein, ΔNp63, and dysregulates epidermal differentiation in a reconstituted human skin model, resulting in the appearance of proliferating keratinocytes even in the uppermost layers of the skin. We verified that, among the amino acid residues in its Zn-binding motif, Cys205 is critical for the processing and nuclear distribution of ΔNp63 and, therefore, Zn-dependent transcriptional activity. Our results suggest that ZIP4 is essential for maintaining human epidermal homeostasis through the regulation of Zn-dependent ΔNp63 activity and can provide insight into the molecular mechanisms responsible for the cutaneous symptoms observed in Acrodermatitis enteropathica patients. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|