Inflammation and Fibrosis in Progeria: Organ-Specific Responses in an HGPS Mouse Model.
Int J Mol Sci
; 25(17)2024 Aug 28.
Article
em En
| MEDLINE
| ID: mdl-39273272
ABSTRACT
Hutchinson-Gilford Progeria Syndrome (HGPS) is an extremely rare genetic disorder that causes accelerated aging, due to a pathogenic variant in the LMNA gene. This pathogenic results in the production of progerin, a defective protein that disrupts the nuclear lamina's structure. In our study, we conducted a histopathological analysis of various organs in the LmnaG609G/G609G mouse model, which is commonly used to study HGPS. The objective of this study was to show that progerin accumulation drives systemic but organ-specific tissue damage and accelerated aging phenotypes. Our findings show significant fibrosis, inflammation, and dysfunction in multiple organ systems, including the skin, cardiovascular system, muscles, lungs, liver, kidneys, spleen, thymus, and heart. Specifically, we observed severe vascular fibrosis, reduced muscle regeneration, lung tissue remodeling, depletion of fat in the liver, and disruptions in immune structures. These results underscore the systemic nature of the disease and suggest that chronic inflammation and fibrosis play crucial roles in the accelerated aging seen in HGPS. Additionally, our study highlights that each organ responds differently to the toxic effects of progerin, indicating that there are distinct mechanisms of tissue-specific damage.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Progéria
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Fibrose
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Lamina Tipo A
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Modelos Animais de Doenças
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Inflamação
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article