ArticleThe Journal of investigative dermatology2017
Stress Signals, Mediated by Membranous Glucocorticoid Receptor, Activate PLC/PKC/GSK-3β/β-catenin Pathway to Inhibit Wound Closure.
Article in The Journal of investigative dermatology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
48 citing papers in PubMed, 1 synthesis or guideline pooled it, 75 citations in OpenAlex.
- MicroRNAs expressed during normal wound healing and their associated pathways: A systematic review and bioinformatics analysis.PloS one · 2023Pooled it
- Topical sodium valproate-loaded nanospanlastics versus conventional topical steroid therapy in alopecia areata: a randomized controlled study.Archives of dermatological research · 2024Trial
- NLRP3 inflammasome activation is associated with type 1 inflammation and neutrophil activation in pyoderma gangrenosum across human and murine models.JID innovations : skin science from molecules to population health · 2026Article
- Abnormally Elevated PKCδ Delays Diabetic Wound Healing by Inhibiting the GAD1-GABA Pathway.Diabetes & metabolism journal · 2026Article
- Inter-Organ Communication Networks in Systemic Physiology: Glucocorticoid Receptor α as a Central Integrator of Homeostasis.International journal of molecular sciences · 2026Review
- NR3C1 Modulates Wnt Signalling to Influence the Invasiveness and Immune Features of Nonfunctioning Invasive Pituitary Adenomas.Journal of cellular and molecular medicine · 2026Article
- Neuro-immuno-endocrinology of the skin: how environment regulates body homeostasis.Nature reviews. Endocrinology · 2025Review
- A Marine-Derived Steroid fromMarine drugs · 2025Article
- Optimized inner ear organoids for efficient hair cell generation and ototoxicity response modeling.Science China. Life sciences · 2025Article
- IGF-1 and Glucocorticoid Receptors Are Potential Target Proteins for the NGF-Mimic Effect ofInternational journal of molecular sciences · 2024Article
- Molecular Pathophysiology of Chronic Wounds: Current State and Future Directions.Cold Spring Harbor perspectives in biology · 2023Review
- Calreticulin: a multifunctional protein with potential therapeutic applications for chronic wounds.Frontiers in medicine · 2023Review
- The NIDDK Diabetic Foot Consortium.Journal of diabetes science and technology · 2023Article
- Local Glucocorticoid Administration Impairs Embryonic Wound Healing.Biomedicines · 2022Article
- Neuroendocrine signaling in the skin with a special focus on the epidermal neuropeptides.American journal of physiology. Cell physiology · 2022Review
- The myeloid mineralocorticoid receptor regulates dermal angiogenesis and inflammation in glucocorticoid-induced impaired wound healing.British journal of pharmacology · 2022Article
- Article
- [Advances on the research and treatment of autoimmune disease-related chronic wounds].Zhonghua shao shang yu chuang mian xiu fu za zhi · 2022Review
- Advanced Wound Diagnostics: Toward Transforming Wound Care into Precision Medicine.Advances in wound care · 2022Review
- Catalase, a therapeutic target in the reversal of estrogen-mediated aging.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.