دورية أكاديمية
Plectin Deficiency in Fibroblasts Deranges Intermediate Filament and Organelle Morphology, Migration, and Adhesion.
| العنوان: | Plectin Deficiency in Fibroblasts Deranges Intermediate Filament and Organelle Morphology, Migration, and Adhesion. |
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| المؤلفون: | Zrelski MM; Department of Cell and Developmental Biology, Center for Anatomy and Cell Biology, Medical University of Vienna, Vienna, Austria., Hösele S; Department of Cell and Developmental Biology, Center for Anatomy and Cell Biology, Medical University of Vienna, Vienna, Austria., Kustermann M; Department of Cell and Developmental Biology, Center for Anatomy and Cell Biology, Medical University of Vienna, Vienna, Austria., Fichtinger P; Department of Cell and Developmental Biology, Center for Anatomy and Cell Biology, Medical University of Vienna, Vienna, Austria., Kah D; Center for Medical Physics and Technology, Department of Physics, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany., Athanasiou I; Department of Dermatology, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Esser PR; Department of Dermatology, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Wagner A; Core Facility Proteomics, Medical University of Vienna, Vienna, Austria; Division of Pediatric Nephrology and Gastroenterology, Department of Pediatrics and Adolescent Medicine, Comprehensive Center for Pediatrics, Medical University of Vienna, Vienna, Austria; Christian Doppler Laboratory for Molecular Stress Research in Peritoneal Dialysis, Division of Pediatric Nephrology and Gastroenterology, Department of Pediatrics and Adolescent Medicine, Comprehensive Center for Pediatrics, Medical University of Vienna, Austria., Herzog R; Division of Pediatric Nephrology and Gastroenterology, Department of Pediatrics and Adolescent Medicine, Comprehensive Center for Pediatrics, Medical University of Vienna, Vienna, Austria; Christian Doppler Laboratory for Molecular Stress Research in Peritoneal Dialysis, Division of Pediatric Nephrology and Gastroenterology, Department of Pediatrics and Adolescent Medicine, Comprehensive Center for Pediatrics, Medical University of Vienna, Austria., Kratochwill K; Core Facility Proteomics, Medical University of Vienna, Vienna, Austria; Division of Pediatric Nephrology and Gastroenterology, Department of Pediatrics and Adolescent Medicine, Comprehensive Center for Pediatrics, Medical University of Vienna, Vienna, Austria; Christian Doppler Laboratory for Molecular Stress Research in Peritoneal Dialysis, Division of Pediatric Nephrology and Gastroenterology, Department of Pediatrics and Adolescent Medicine, Comprehensive Center for Pediatrics, Medical University of Vienna, Austria., Goldmann WH; Center for Medical Physics and Technology, Department of Physics, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany., Kiritsi D; Department of Dermatology, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Winter L; Department of Cell and Developmental Biology, Center for Anatomy and Cell Biology, Medical University of Vienna, Vienna, Austria. Electronic address: lilli.winter@meduniwien.ac.at. |
| المصدر: | The Journal of investigative dermatology [J Invest Dermatol] 2024 Mar; Vol. 144 (3), pp. 547-562.e9. Date of Electronic Publication: 2023 Sep 15. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: United States NLM ID: 0426720 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1523-1747 (Electronic) Linking ISSN: 0022202X NLM ISO Abbreviation: J Invest Dermatol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2016- : New York : Elsevier Original Publication: Baltimore, Williams & Wilkins. |
| مواضيع طبية MeSH: | Epidermolysis Bullosa Simplex*/pathology , Muscular Dystrophies*/complications , Muscular Dystrophies*/genetics , Muscular Dystrophies*/metabolism , Muscular Dystrophies, Limb-Girdle*, Humans ; Intermediate Filaments/metabolism ; Plectin/genetics ; Mitochondria/metabolism ; Fibroblasts/metabolism ; Intermediate Filament Proteins/metabolism |
| مستخلص: | Plectin, a highly versatile and multifunctional cytolinker, has been implicated in several multisystemic disorders. Most sequence variations in the human plectin gene (PLEC) cause epidermolysis bullosa simplex with muscular dystrophy (EBS-MD), an autosomal recessive skin-blistering disorder associated with progressive muscle weakness. In this study, we performed a comprehensive cell biological analysis of dermal fibroblasts from three different patients with EBS-MD, where PLEC expression analyses revealed preserved mRNA levels in all cases, whereas full-length plectin protein content was significantly reduced or completely absent. Downstream effects of pathogenic PLEC sequence alterations included massive bundling of vimentin intermediate filament networks, including the occurrence of ring-like nuclei-encasing filament bundles, elongated mitochondrial networks, and abnormal nuclear morphologies. We found that essential fibroblast functions such as wound healing, migration, or orientation upon cyclic stretch were significantly impaired in the cells of patients with EBS-MD. Finally, EBS-MD fibroblasts displayed reduced adhesion capacities, which could be attributed to smaller focal adhesion contacts. Our study not only emphasizes plectin's functional role in human skin fibroblasts, it also provides further insights into the understanding of EBS-MD-associated disease mechanisms. (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.) |
| معلومات مُعتمدة: | I 6049 Austria FWF_ Austrian Science Fund FWF; P 31541 Austria FWF_ Austrian Science Fund FWF |
| المشرفين على المادة: | 0 (Plectin) 0 (Intermediate Filament Proteins) |
| SCR Disease Name: | Epidermolysa bullosa simplex and limb girdle muscular dystrophy |
| تواريخ الأحداث: | Date Created: 20230916 Date Completed: 20240226 Latest Revision: 20240417 |
| رمز التحديث: | 20240417 |
| DOI: | 10.1016/j.jid.2023.08.020 |
| PMID: | 37716646 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1523-1747 |
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| DOI: | 10.1016/j.jid.2023.08.020 |