دورية أكاديمية
Conditional knock out of N-WASP in keratinocytes causes skin barrier defects and atopic dermatitis-like inflammation.
العنوان: | Conditional knock out of N-WASP in keratinocytes causes skin barrier defects and atopic dermatitis-like inflammation. |
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المؤلفون: | Kalailingam P; School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore, 637551, Republic of Singapore., Tan HB; School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore, 637551, Republic of Singapore., Jain N; School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore, 637551, Republic of Singapore., Sng MK; School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore, 637551, Republic of Singapore.; Lee Kong Chian School of Medicine, Nanyang Technological University, 59 Nanyang Avenue, Singapore, 636921, Republic of Singapore., Chan JSK; School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore, 637551, Republic of Singapore., Tan NS; School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore, 637551, Republic of Singapore.; Lee Kong Chian School of Medicine, Nanyang Technological University, 59 Nanyang Avenue, Singapore, 636921, Republic of Singapore.; Institute of Molecular and Cell Biology, 61 Biopolis Drive, Singapore, 138673, Republic of Singapore.; KK Women's and Children's Hospital, 100 Bukit Timah Road, Singapore, 229899, Republic of Singapore., Thanabalu T; School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore, 637551, Republic of Singapore. thirumaran@ntu.edu.sg. |
المصدر: | Scientific reports [Sci Rep] 2017 Aug 04; Vol. 7 (1), pp. 7311. Date of Electronic Publication: 2017 Aug 04. |
نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: London : Nature Publishing Group, copyright 2011- |
مواضيع طبية MeSH: | Dermatitis, Atopic/*genetics , Dermatitis, Atopic/*metabolism , Epidermis/*metabolism , Keratinocytes/*metabolism , Wiskott-Aldrich Syndrome Protein, Neuronal/*genetics, Animals ; Biomarkers ; Claudin-5/genetics ; Claudin-5/metabolism ; Dermatitis, Atopic/immunology ; Dermatitis, Atopic/pathology ; Epidermis/pathology ; Fibroblast Growth Factor 7/genetics ; Fibroblast Growth Factor 7/metabolism ; Fluorescent Antibody Technique ; Gene Expression ; Hyperplasia ; Mice ; Mice, Knockout ; Phenotype ; Receptors, Platelet-Derived Growth Factor/genetics ; Receptors, Platelet-Derived Growth Factor/metabolism ; Wiskott-Aldrich Syndrome Protein, Neuronal/metabolism |
مستخلص: | Neural-Wiskott Aldrich Syndrome Protein (N-WASP) is expressed ubiquitously and regulates actin cytoskeleton remodeling. In order to characterize the role of N-WASP in epidermal homeostasis and cutaneous biology, we generated conditional N-WASP knockout mouse using CK14-cre (cytokeratin 14) to ablate expression of N-WASP in keratinocytes. N-WASP K14KO (N-WASP fl/fl ; CK14-Cre) mice were born following Mendelian genetics suggesting that N-WASP expression in keratinocytes is not essential during embryogenesis. N-WASP K14KO mice exhibited stunted growth, alopecia, dry and wrinkled skin. The dry skin in N-WASP K14KO mice is probably due to increased transepidermal water loss (TEWL) caused by barrier function defects as revealed by dye penetration assay. N-WASP K14KO mice developed spontaneous inflammation in the neck and face 10 weeks after birth. Histological staining revealed thickening of the epidermis, abnormal cornified layer and extensive infiltration of immune cells (mast cells, eosinophils and T-lymphocytes) in N-WASP K14KO mice skin compared to control mice. N-WASP K14KO mice had higher serum levels of IL-1α, TNF-α, IL-6 and IL-17 compared to control mice. Thus our results suggest that conditional N-WASP knockout in keratinocytes leads to compromised skin barrier, higher infiltration of immune cells and hyperproliferation of keratinocytes due to increased production of cytokines highlighting the importance of N-WASP in maintaining the skin homeostasis. |
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المشرفين على المادة: | 0 (Biomarkers) 0 (Claudin-5) 0 (Fgf7 protein, mouse) 0 (Wiskott-Aldrich Syndrome Protein, Neuronal) 126469-10-1 (Fibroblast Growth Factor 7) EC 2.7.10.1 (Receptors, Platelet-Derived Growth Factor) |
تواريخ الأحداث: | Date Created: 20170806 Date Completed: 20190221 Latest Revision: 20190221 |
رمز التحديث: | 20231215 |
مُعرف محوري في PubMed: | PMC5544743 |
DOI: | 10.1038/s41598-017-07125-8 |
PMID: | 28779153 |
قاعدة البيانات: | MEDLINE |
تدمد: | 2045-2322 |
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DOI: | 10.1038/s41598-017-07125-8 |