کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5649521 | 1407126 | 2017 | 35 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Stress Signals, Mediated by Membranous Glucocorticoid Receptor, Activate PLC/PKC/GSK-3β/β-catenin Pathway to Inhibit Wound Closure
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کلمات کلیدی
DEXHEKGSK-3βPLCPKCDexamethasone - دگزامتازونphospholipase C - فسفولیپاز CProtein kinase C - پروتئین کیناز سیCalphostin C - کالفوستین CHuman keratinocyte - کراتینوسیت انسانGlucocorticoid - گلوکوکورتیکوئیدهاglycogen synthase kinase 3 beta - گلیکوزین سنتاز کیناز 3 بتاglucocorticoid receptor - گیرنده گلوکوکورتیکوئیدGilz - گیلز
موضوعات مرتبط
علوم پزشکی و سلامت
پزشکی و دندانپزشکی
امراض پوستی
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چکیده انگلیسی
Glucocorticoids (GCs), key mediators of stress signals, are also potent wound healing inhibitors. To understand how stress signals inhibit wound healing, we investigated the role of membranous glucocorticoid receptor (mbGR) by using cell-impermeable BSA-conjugated dexamethasone. We found that mbGR inhibits keratinocyte migration and wound closure by activating a Wnt-like phospholipase (PLC)/ protein kinase C (PKC) signaling cascade. Rapid activation of mbGR/PLC/PKC further leads to activation of known biomarkers of nonhealing found in patients, β-catenin and c-myc. Conversely, a selective inhibitor of PKC, calphostin C, blocks mbGR/PKC pathway, and rescues GC-mediated inhibition of keratinocyte migration in vitro and accelerates wound epithelialization of human wounds ex vivo. This novel signaling mechanism may have a major impact on understanding how stress response via GC signaling regulates homeostasis and its role in development and treatments of skin diseases, including wound healing. To test tissue specificity of this nongenomic signaling mechanism, we tested retinal and bronchial human epithelial cells and fibroblasts. We found that mbGR/PLC/PKC signaling cascade exists in all cell types tested, suggesting a more general role. The discovery of this nongenomic signaling pathway, in which glucocorticoids activate Wnt pathway via mbGR, provides new insights into how stress-mediated signals may activate growth signals in various epithelial and mesenchymal tissues.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Investigative Dermatology - Volume 137, Issue 5, May 2017, Pages 1144-1154
Journal: Journal of Investigative Dermatology - Volume 137, Issue 5, May 2017, Pages 1144-1154
نویسندگان
Ivan Jozic, Sasa Vukelic, Olivera Stojadinovic, Liang Liang, Horacio A. Ramirez, Irena Pastar, Marjana Tomic Canic,