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Molecular and Mechanobiological Pathways Related to the Physiopathology of FPLD2
Laminopathies are rare and heterogeneous diseases affecting one to almost all tissues, as in Progeria, and sharing certain features such as metabolic disorders and a predisposition to atherosclerotic cardiovascular diseases. These two features are the main characteristics of the adipose tissue-speci...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7565540/ https://www.ncbi.nlm.nih.gov/pubmed/32842478 http://dx.doi.org/10.3390/cells9091947 |
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author | Varlet, Alice-Anaïs Helfer, Emmanuèle Badens, Catherine |
author_facet | Varlet, Alice-Anaïs Helfer, Emmanuèle Badens, Catherine |
author_sort | Varlet, Alice-Anaïs |
collection | PubMed |
description | Laminopathies are rare and heterogeneous diseases affecting one to almost all tissues, as in Progeria, and sharing certain features such as metabolic disorders and a predisposition to atherosclerotic cardiovascular diseases. These two features are the main characteristics of the adipose tissue-specific laminopathy called familial partial lipodystrophy type 2 (FPLD2). The only gene that is involved in FPLD2 physiopathology is the LMNA gene, with at least 20 mutations that are considered pathogenic. LMNA encodes the type V intermediate filament lamin A/C, which is incorporated into the lamina meshwork lining the inner membrane of the nuclear envelope. Lamin A/C is involved in the regulation of cellular mechanical properties through the control of nuclear rigidity and deformability, gene modulation and chromatin organization. While recent studies have described new potential signaling pathways dependent on lamin A/C and associated with FPLD2 physiopathology, the whole picture of how the syndrome develops remains unknown. In this review, we summarize the signaling pathways involving lamin A/C that are associated with the progression of FPLD2. We also explore the links between alterations of the cellular mechanical properties and FPLD2 physiopathology. Finally, we introduce potential tools based on the exploration of cellular mechanical properties that could be redirected for FPLD2 diagnosis. |
format | Online Article Text |
id | pubmed-7565540 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-75655402020-10-26 Molecular and Mechanobiological Pathways Related to the Physiopathology of FPLD2 Varlet, Alice-Anaïs Helfer, Emmanuèle Badens, Catherine Cells Review Laminopathies are rare and heterogeneous diseases affecting one to almost all tissues, as in Progeria, and sharing certain features such as metabolic disorders and a predisposition to atherosclerotic cardiovascular diseases. These two features are the main characteristics of the adipose tissue-specific laminopathy called familial partial lipodystrophy type 2 (FPLD2). The only gene that is involved in FPLD2 physiopathology is the LMNA gene, with at least 20 mutations that are considered pathogenic. LMNA encodes the type V intermediate filament lamin A/C, which is incorporated into the lamina meshwork lining the inner membrane of the nuclear envelope. Lamin A/C is involved in the regulation of cellular mechanical properties through the control of nuclear rigidity and deformability, gene modulation and chromatin organization. While recent studies have described new potential signaling pathways dependent on lamin A/C and associated with FPLD2 physiopathology, the whole picture of how the syndrome develops remains unknown. In this review, we summarize the signaling pathways involving lamin A/C that are associated with the progression of FPLD2. We also explore the links between alterations of the cellular mechanical properties and FPLD2 physiopathology. Finally, we introduce potential tools based on the exploration of cellular mechanical properties that could be redirected for FPLD2 diagnosis. MDPI 2020-08-23 /pmc/articles/PMC7565540/ /pubmed/32842478 http://dx.doi.org/10.3390/cells9091947 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Varlet, Alice-Anaïs Helfer, Emmanuèle Badens, Catherine Molecular and Mechanobiological Pathways Related to the Physiopathology of FPLD2 |
title | Molecular and Mechanobiological Pathways Related to the Physiopathology of FPLD2 |
title_full | Molecular and Mechanobiological Pathways Related to the Physiopathology of FPLD2 |
title_fullStr | Molecular and Mechanobiological Pathways Related to the Physiopathology of FPLD2 |
title_full_unstemmed | Molecular and Mechanobiological Pathways Related to the Physiopathology of FPLD2 |
title_short | Molecular and Mechanobiological Pathways Related to the Physiopathology of FPLD2 |
title_sort | molecular and mechanobiological pathways related to the physiopathology of fpld2 |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7565540/ https://www.ncbi.nlm.nih.gov/pubmed/32842478 http://dx.doi.org/10.3390/cells9091947 |
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