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ANTXR1 deficiency promotes fibroblast senescence: implications for GAPO syndrome as a progeroid disorder.
Przyklenk, Matthias; Karmacharya, Shreya; Bonasera, Debora; Pasanen-Zentz, Arthur-Lauri; Kmoch, Stanislav; Paulsson, Mats; Wagener, Raimund; Liccardi, Gianmaria; Schiavinato, Alvise.
Afiliación
  • Przyklenk M; Center for Biochemistry, Medical Faculty, University of Cologne, Joseph-Stelzmann-Str. 52, 50931, Cologne, Germany.
  • Karmacharya S; Center for Biochemistry, Medical Faculty, University of Cologne, Joseph-Stelzmann-Str. 52, 50931, Cologne, Germany.
  • Bonasera D; Genetic Instability, Cell Death and Inflammation Laboratory, Center for Biochemistry, Medical Faculty, University of Cologne, Joseph-Stelzmann-Str. 52, 50931, Cologne, Germany.
  • Pasanen-Zentz AL; Center for Biochemistry, Medical Faculty, University of Cologne, Joseph-Stelzmann-Str. 52, 50931, Cologne, Germany.
  • Kmoch S; Research Unit of Rare Diseases, Department of Pediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University, Prague, Czech Republic.
  • Paulsson M; Center for Biochemistry, Medical Faculty, University of Cologne, Joseph-Stelzmann-Str. 52, 50931, Cologne, Germany.
  • Wagener R; Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.
  • Liccardi G; Center for Biochemistry, Medical Faculty, University of Cologne, Joseph-Stelzmann-Str. 52, 50931, Cologne, Germany.
  • Schiavinato A; Genetic Instability, Cell Death and Inflammation Laboratory, Center for Biochemistry, Medical Faculty, University of Cologne, Joseph-Stelzmann-Str. 52, 50931, Cologne, Germany.
Sci Rep ; 14(1): 9321, 2024 04 23.
Article en En | MEDLINE | ID: mdl-38653789
ABSTRACT
ANTXR1 is one of two cell surface receptors mediating the uptake of the anthrax toxin into cells. Despite substantial research on its role in anthrax poisoning and a proposed function as a collagen receptor, ANTXR1's physiological functions remain largely undefined. Pathogenic variants in ANTXR1 lead to the rare GAPO syndrome, named for its four primary features Growth retardation, Alopecia, Pseudoanodontia, and Optic atrophy. The disease is also associated with a complex range of other phenotypes impacting the cardiovascular, skeletal, pulmonary and nervous systems. Aberrant accumulation of extracellular matrix components and fibrosis are considered to be crucial components in the pathogenesis of GAPO syndrome, contributing to the shortened life expectancy of affected individuals. Nonetheless, the specific mechanisms connecting ANTXR1 deficiency to the clinical manifestations of GAPO syndrome are largely unexplored. In this study, we present evidence that ANTXR1 deficiency initiates a senescent phenotype in human fibroblasts, correlating with defects in nuclear architecture and actin dynamics. We provide novel insights into ANTXR1's physiological functions and propose GAPO syndrome to be reconsidered as a progeroid disorder highlighting an unexpected role for an integrin-like extracellular matrix receptor in human aging.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Senescencia Celular / Alopecia / Fibroblastos / Trastornos del Crecimiento / Anodoncia / Proteínas de Microfilamentos Límite: Humans Idioma: En Revista: Sci Rep Año: 2024 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Senescencia Celular / Alopecia / Fibroblastos / Trastornos del Crecimiento / Anodoncia / Proteínas de Microfilamentos Límite: Humans Idioma: En Revista: Sci Rep Año: 2024 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Reino Unido