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EMILIN1 deficiency causes arterial tortuosity with osteopenia and connects impaired elastogenesis with defective collagen fibrillogenesis

التفاصيل البيبلوغرافية
العنوان: EMILIN1 deficiency causes arterial tortuosity with osteopenia and connects impaired elastogenesis with defective collagen fibrillogenesis
المؤلفون: Adamo, C. S., Beyens, A., Schiavinato, A., Keene, D. R., Tufa, S. F., Mörgelin, M., Brinckmann, J., Sasaki, T., Niehoff, A., Dreiner, M., Pottie, L., Muiño-Mosquera, L., Gulec, E. Y., Gezdirici, A., Braghetta, P., Bonaldo, P., Wagener, R., Paulsson, M., Bornaun, H., De Rycke, R., De Bruyne, M., Baeke, F., Devine, W. P., Gangaram, B., Tam, A., Balasubramanian, M., Ellard, S., Moore, S., Symoens, S., Shen, J., Cole, S., Schwarze, U., Holmes, K. W., Hayflick, S. J., Wiszniewski, W., Nampoothiri, S., Davis, E. C., Sakai, L. Y., Sengle, G., Callewaert, B.
بيانات النشر: Cell Press
سنة النشر: 2023
المجموعة: RD&E Research Repository (Royal Devon and Exeter NHS Foundation Trust)
مصطلحات موضوعية: Humans, Mice, Animals, Cutis Laxa/genetics, Elastin/metabolism, Extracellular Matrix Proteins/metabolism, Collagen/genetics, Bone Diseases, Metabolic, Efemp2, Emilin1, Lox, aortic aneurysm, arterial tortuosity, collagen, cutis laxa, elastic fiber, extracellular matrix, fracture
الوصف: EMILIN1 (elastin-microfibril-interface-located-protein-1) is a structural component of the elastic fiber network and localizes to the interface between the fibrillin microfibril scaffold and the elastin core. How EMILIN1 contributes to connective tissue integrity is not fully understood. Here, we report bi-allelic EMILIN1 loss-of-function variants causative for an entity combining cutis laxa, arterial tortuosity, aneurysm formation, and bone fragility, resembling autosomal-recessive cutis laxa type 1B, due to EFEMP2 (FBLN4) deficiency. In both humans and mice, absence of EMILIN1 impairs EFEMP2 extracellular matrix deposition and LOX activity resulting in impaired elastogenesis, reduced collagen crosslinking, and aberrant growth factor signaling. Collagen fiber ultrastructure and histopathology in EMILIN1- or EFEMP2-deficient skin and aorta corroborate these findings and murine Emilin1(-/-) femora show abnormal trabecular bone formation and strength. Altogether, EMILIN1 connects elastic fiber network with collagen fibril formation, relevant for both bone and vascular tissue homeostasis. ; The article is available via Open Access. Click on the 'Additional link' above to access the full-text. ; Published version, accepted version (6 month embargo), submitted version
نوع الوثيقة: article in journal/newspaper
اللغة: English
العلاقة: https://linkinghub.elsevier.com/retrieve/pii/S0002-9297Test(22)00458-X; Am J Hum Genet. 2022 Dec 1;109(12):2230-2252. doi:10.1016/j.ajhg.2022.10.010. Epub 2022 Nov 8.; https://rde.dspace-express.com/handle/11287/622695Test; American journal of human genetics
DOI: 10.1016/j.ajhg.2022.10.010
الإتاحة: https://doi.org/10.1016/j.ajhg.2022.10.010Test
https://rde.dspace-express.com/handle/11287/622695Test
حقوق: Copyright © 2022 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved. ; http://creativecommons.org/publicdomain/zero/1.0Test/
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قاعدة البيانات: BASE
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