دورية أكاديمية
أعرض في EDS

Glucocorticoids activate Yes-associated protein in human vocal fold fibroblasts.

التفاصيل البيبلوغرافية
العنوان: Glucocorticoids activate Yes-associated protein in human vocal fold fibroblasts.
المؤلفون: Nakamura R; Department of Rehabilitation Medicine, NYU Grossman School of Medicine, New York, NY, USA., Bing R; Department of Rehabilitation Medicine, NYU Grossman School of Medicine, New York, NY, USA., Doyle CP; Department of Rehabilitation Medicine, NYU Grossman School of Medicine, New York, NY, USA., Garabedian MJ; Department of Microbiology, NYU Grossman School of Medicine, New York, NY, USA., Branski RC; Department of Rehabilitation Medicine, NYU Grossman School of Medicine, New York, NY, USA; Department of Otolaryngology-Head and Neck Surgery, NYU Grossman School of Medicine, New York, NY, USA. Electronic address: ryan.branski@nyulangone.org.
المصدر: Experimental cell research [Exp Cell Res] 2021 Aug 15; Vol. 405 (2), pp. 112681. Date of Electronic Publication: 2021 Jun 02.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural
اللغة: English
بيانات الدورية: Publisher: Academic Press Country of Publication: United States NLM ID: 0373226 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1090-2422 (Electronic) Linking ISSN: 00144827 NLM ISO Abbreviation: Exp Cell Res Subsets: MEDLINE
أسماء مطبوعة: Publication: Orlando Fl : Academic Press
Original Publication: New York, Academic Press.
مواضيع طبية MeSH: Fibroblasts/*drug effects , Gene Expression/*drug effects , Glucocorticoids/*pharmacology , Protein Transport/*drug effects, Humans ; Phosphorylation/drug effects ; Transcriptional Activation/drug effects ; Wnt Signaling Pathway/drug effects
مستخلص: Fibrosis of the vocal folds poses a substantive clinical challenge potentially underlying the rapid proliferation of direct steroid injections into the upper airway. The variable clinical response to glucocorticoids (GCs) in the vocal folds is likely related to diversity inherent to GCs and patient-specific, and upstream, cell-specific responses to GCs. Broadly, we hypothesize the disparity in clinical outcomes are due to undesirable effects of GCs on resident fibroblasts. Transcriptome analysis identified significant GC-mediated modulation of Hippo signaling, a known regulator of fibrotic gene expression. Subsequent analysis confirmed GC-mediated YAP activation, a transcriptional co-factor in the Hippo signaling pathway. YAP inhibition attenuated ACTA2 expression in GC-treated human vocal fold fibroblasts. Nuclear localization and phosphorylation at Ser211, however, was not affected by YAP inhibition, suggesting nuclear translocation of YAP is indirectly driven by GR. RNA-seq analysis confirmed the influence of GCs on Wnt signaling, and canonical Wnt signaling target genes were upregulated by GCs. These data implicate YAP and its downstream targets as putative mediators of a pro-fibrotic response to GCs. Therapeutic YAP inhibition may ultimately be clinically relevant and warrants further consideration.
(Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)
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معلومات مُعتمدة: R01 DC017397 United States DC NIDCD NIH HHS
فهرسة مساهمة: Keywords: Fibrosis; Glucocorticoid; Hippo; Vocal fold; YAP
المشرفين على المادة: 0 (Glucocorticoids)
تواريخ الأحداث: Date Created: 20210604 Date Completed: 20211011 Latest Revision: 20220816
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC8328950
DOI: 10.1016/j.yexcr.2021.112681
PMID: 34087241
قاعدة البيانات: MEDLINE
الوصف
تدمد:1090-2422
DOI:10.1016/j.yexcr.2021.112681