A p.C217R Mutation in Fibulin-5 from Cutis Laxa Patients Is Associated with Incomplete Extracellular Matrix Formation in a Skin Equivalent Model
| العنوان: | A p.C217R Mutation in Fibulin-5 from Cutis Laxa Patients Is Associated with Incomplete Extracellular Matrix Formation in a Skin Equivalent Model |
|---|---|
| المؤلفون: | Romain Debret, Florence Jobard, Safa Saker, Odile Damour, Judith Fischer, Pascal Sommer, André Mégarbané, Stephanie Claus, Hala Mégarbané, Martine Devillers, Simone Peyrol |
| المساهمون: | Centre National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Service de dermatologie, Saint Georges Hospital, Institut Jérôme Lejeune, Laboratoire de Biologie Tissulaire et d'ingénierie Thérapeutique UMR 5305 (LBTI), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), IFR Laennec (IL), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Banque d’ADN et de Cellules, Généthon, Université Paris Descartes - Paris 5 (UPD5), Deleage, Gilbert, Institut de biologie et chimie des protéines [Lyon] (IBCP), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) |
| المصدر: | Journal of Investigative Dermatology Journal of Investigative Dermatology, 2008, 128 (6), pp.1442-1450. ⟨10.1038/sj.jid.5701211⟩ Journal of Investigative Dermatology, Nature Publishing Group, 2008, xxx, pp.1442-1450 Journal of Investigative Dermatology, Nature Publishing Group, 2008, 128 (6), pp.1442-1450. ⟨10.1038/sj.jid.5701211⟩ |
| بيانات النشر: | HAL CCSD, 2008. |
| سنة النشر: | 2008 |
| مصطلحات موضوعية: | Male, Pathology, medicine.medical_specialty, Collagen Type VII, [SDV]Life Sciences [q-bio], DNA Mutational Analysis, Mutation, Missense, Dermatology, Models, Biological, Biochemistry, Basement Membrane, Cutis Laxa, Extracellular matrix, 03 medical and health sciences, 0302 clinical medicine, Dermis, medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Humans, Skin equivalent, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Molecular Biology, Skin, 030304 developmental biology, Basement membrane, Extracellular Matrix Proteins, 0303 health sciences, business.industry, Homozygote, Genodermatosis, Cell Biology, Fibroblasts, medicine.disease, Extracellular Matrix, 3. Good health, Fibulin, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Mutation, Female, business, Elastic fiber, Cutis laxa |
| الوصف: | International audience; Cutis laxa (CL) is a rare genodermatosis, which is clinically and genetically heterogeneous. It is characterized by redundant, loose, sagging, and inelastic skin. In a consanguineous family from Lebanon with autosomal-recessive transmission, we identified a homozygous missense mutation (c.649T --> C; p.C217R) in the fibulin-5 gene (FBLN5), which was, to our knowledge, previously unreported. Small skin biopsies were performed, which permitted isolation of skin fibroblasts harboring this FBLN5 mutation; they exhibited a deficit in cell growth. A CL skin equivalent (CL-SE) model compared with control SE was successfully developed to define the behavior of CL fibroblasts in a three-dimensional model. There was increased cell death and a global extracellular matrix deficiency in the dermis of this CL-SE model, and a low level of the main elastic fiber expression. There was no basement membrane evident at the ultrastructural level, and type-VII collagen could not be detected at the histological level. This model reproduced some defects of the extracellular matrix and highlighted other defects, which occurred at the time of the basement membrane formation, which were not evident in skin from patients. This CL-SE model could be adapted to screen for therapeutically active molecules.Cutis laxa (CL) is a rare genodermatosis, which is clinically and genetically heterogeneous. It is characterized by redundant, loose, sagging, and inelastic skin. In a consanguineous family from Lebanon with autosomal-recessive transmission, we identified a homozygous missense mutation (c.649T --> C; p.C217R) in the fibulin-5 gene (FBLN5), which was, to our knowledge, previously unreported. Small skin biopsies were performed, which permitted isolation of skin fibroblasts harboring this FBLN5 mutation; they exhibited a deficit in cell growth. A CL skin equivalent (CL-SE) model compared with control SE was successfully developed to define the behavior of CL fibroblasts in a three-dimensional model. There was increased cell death and a global extracellular matrix deficiency in the dermis of this CL-SE model, and a low level of the main elastic fiber expression. There was no basement membrane evident at the ultrastructural level, and type-VII collagen could not be detected at the histological level. This model reproduced some defects of the extracellular matrix and highlighted other defects, which occurred at the time of the basement membrane formation, which were not evident in skin from patients. This CL-SE model could be adapted to screen for therapeutically active molecules. |
| اللغة: | English |
| تدمد: | 0022-202X 1523-1747 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::390e54b932f72575dd3c490b2d15e713Test https://hal.science/hal-02340184Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....390e54b932f72575dd3c490b2d15e713 |
| قاعدة البيانات: | OpenAIRE |
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In a consanguineous family from Lebanon with autosomal-recessive transmission, we identified a homozygous missense mutation (c.649T --> C; p.C217R) in the fibulin-5 gene (FBLN5), which was, to our knowledge, previously unreported. Small skin biopsies were performed, which permitted isolation of skin fibroblasts harboring this FBLN5 mutation; they exhibited a deficit in cell growth. A CL skin equivalent (CL-SE) model compared with control SE was successfully developed to define the behavior of CL fibroblasts in a three-dimensional model. There was increased cell death and a global extracellular matrix deficiency in the dermis of this CL-SE model, and a low level of the main elastic fiber expression. There was no basement membrane evident at the ultrastructural level, and type-VII collagen could not be detected at the histological level. This model reproduced some defects of the extracellular matrix and highlighted other defects, which occurred at the time of the basement membrane formation, which were not evident in skin from patients. This CL-SE model could be adapted to screen for therapeutically active molecules.Cutis laxa (CL) is a rare genodermatosis, which is clinically and genetically heterogeneous. It is characterized by redundant, loose, sagging, and inelastic skin. In a consanguineous family from Lebanon with autosomal-recessive transmission, we identified a homozygous missense mutation (c.649T --> C; p.C217R) in the fibulin-5 gene (FBLN5), which was, to our knowledge, previously unreported. Small skin biopsies were performed, which permitted isolation of skin fibroblasts harboring this FBLN5 mutation; they exhibited a deficit in cell growth. A CL skin equivalent (CL-SE) model compared with control SE was successfully developed to define the behavior of CL fibroblasts in a three-dimensional model. There was increased cell death and a global extracellular matrix deficiency in the dermis of this CL-SE model, and a low level of the main elastic fiber expression. There was no basement membrane evident at the ultrastructural level, and type-VII collagen could not be detected at the histological level. This model reproduced some defects of the extracellular matrix and highlighted other defects, which occurred at the time of the basement membrane formation, which were not evident in skin from patients. 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|
| IllustrationInfo |