Iron accumulation drives fibrosis, senescence and the senescence-associated secretory phenotype
Fibrogenesis is part of a normal protective response to tissue injury that can become irreversible and progressive, leading to fatal diseases. Senescent cells are a main driver of fibrotic diseases through their secretome, known as senescence-associated secretory phenotype (SASP). Here, we report that cellular senescence, and multiple types of fibrotic diseases in mice and humans are characterized by the accumulation of iron. We show that vascular and hemolytic injuries are efficient in triggering iron accumulation, which in turn can cause senescence and promote fibrosis. Notably, we find that senescent cells persistently accumulate iron, even when the surge of extracellular iron has subdued. Indeed, under normal conditions of extracellular iron, cells exposed to different types of senescence-inducing insults accumulate abundant ferritin-bound iron, mostly within lysosomes, and present high levels of labile iron, which fuels the generation of reactive oxygen species and the SASP. Finally, we demonstrate that detection of iron by magnetic resonance imaging might allow non-invasive assessment of fibrotic burden in the kidneys of mice and in patients with renal fibrosis. Our findings suggest that iron accumulation plays a central role in senescence and fibrosis, even when the initiating events may be independent of iron, and identify iron metabolism as a potential therapeutic target for senescence-associated diseases.
Puedes leer el artículo completo aquí: https://www.nature.com/articles/s42255-023-00928-2
Authors: Mate Maus, Vanessa López-Polo, Lidia Mateo, Miguel Lafarga, Mònica Aguilera, Eugenia De Lama, Kathleen Meyer, Anna Sola, Cecilia Lopez-Martinez, Ines López-Alonso, Marc Guasch-Piqueras, Fernanda Hernandez-Gonzalez, Selim Chaib, Miguel Rovira, Mayka Sanchez, Rosa Faner, Alvar Agusti, Rodrigo Diéguez-Hurtado, Sagrario Ortega, Anna Manonelles, Stefan Engelhardt, Freddy Monteiro, Camille Stephan-Otto Attolini, Neus Prats, Guillermo Albaiceta, Josep M. Cruzado & Manuel Serrano
To investigate it, we calculated immune signatures with Gene Set Variation Analysis (GSVA) and applied them to the lung transcriptome followed by unbiased cluster analysis of GSVA immune-enrichment scores, in 109 IPF patients from the Lung Tissue Research Consortium (LTRC)
A new research paper was published on the cover of Aging (listed by MEDLINE/PubMed as «Aging (Albany NY)» and «Aging-US» by Web of Science) Volume 15, Issue 14, entitled, «Human senescent fibroblasts trigger progressive lung fibrosis in mice.»
Syndrome of Combined Pulmonary Fibrosis and Emphysema: An Official ATS/ERS/JRS/ALAT Research Statement
The objectives of this task force were to review the terminology, definition, characteristics, pathophysiology, and research priorities of CPFE and to explore whether CPFE is a syndrome.
Recuerda que puedes acceder a varios enlaces a artículos dentro de la categoría Fibrosis en esta web. También puedes acceder otros enlaces en el Listado de Artículos de la Cátedra de Salud Respiratoria.
Imagen obtenida en artículo original.