ArticleJournal of molecular medicine (Berlin, Germany)2025
Ferroptosis and iron metabolism drive fibroblast activation in silicosis: insights from a novel 3D lung matrix model.
Article in Journal of molecular medicine (Berlin, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors.
Funding
Abstract
backgroundSilicosis is a lung disease marked by fibrosis and nodule formation, yet the impact of iron metabolism on these processes remains unclear. Existing models lack the ability to replicate the microenvironmental complexity needed to study iron-driven fibroblast activity. This study aimed to explore the role of iron metabolism in the progression of silicosis using a novel in vitro 3D culture system.
methodsIn this study, a 3D spheroid model was established using lung decellularized matrix (LDM) particles and murine lung fibroblasts (NIH/3T3). Silica-stimulated macrophage supernatant was added to simulate fibrotic conditions. Histological staining, RNA sequencing, and iron quantification were conducted to investigate matrix production, fibroblast proliferation, and oxidative stress dynamics. Two ferroptosis inhibitors, deferoxamine (DFO) and ferrostatin-1 (Fer-1), were utilized to clarify the impact of iron metabolism on fibrotic processes.
resultsThe LDM-supported spheroid model successfully mimicked in vivo-like conditions. Histological analysis confirmed that LDM improved fibroblast viability and preserved extracellular matrix architecture. Silica-stimulated spheroids showed enhanced fibroblast proliferation, matrix production, and altered iron metabolism. Iron accumulation was associated with increased oxidative stress and disrupted Nrf2-SLC7A11 signaling. The addition of DFO inhibited fibroblast proliferation, while Fer-1 promoted it, highlighting the dual effects of iron metabolism on fibrotic progression.
conclusionsThis study highlights the dual role of iron metabolism in the regulation of fibroblast activity and extracellular matrix dynamics. The 3D spheroid model provides a novel platform to elucidate silicosis pathogenesis and advance antifibrotic therapeutic strategies. KEY MESSAGES: A novel 3D model to study silicotic nodule formation and fibroblast activation. LDM and silica-stimulated supernatants promote fibroblast proliferation around spheroids. Silica exposure induces unique cell death patterns, with ferroptosis as a key mechanism. Disruption of Nrf2/SLC7A11/GPX4 axis links ferroptosis to fibrosis progression. Iron metabolism influences fibroblast activity and ferroptosis in silicosis.
Indexed as
Identifiers
40796985What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.