The Role of Activated Stromal Cells in Fibrotic Foci Formation and Reversion

Fibrotic focus is a pivotal morphofunctional unit in developing fibrosis in various tissues. For most fibrotic diseases, including progressive forms, the foci are considered unable to remodel and contribute to the worsening of prognosis. Unfortunately, the dynamics of the fibrotic focus formation an...

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Published in:Cells (Basel, Switzerland) Switzerland), 2024-12, Vol.13 (24), p.2064
Main Authors: Basalova, Nataliya Andreevna, Vigovskiy, Maksim Alexandrovich, Popov, Vladimir Sergeevich, Lagereva, Evgeniya Alexandrovna, Grigorieva, Olga Alexandrovna, Efimenko, Anastasia Yuryevna
Format: Article
Language:English
Subjects:
activated stromal cells
Anesthesia
Animal models
Animals
Antibodies
Bleomycin
CD90 (THY-1)
Connective tissue
Ethylenediaminetetraacetic acid
Evaluation
Extracellular matrix
FAPα
fibroblast activation protein
Fibroblasts
Fibrosis
Functional morphology
Lungs
Macrophages
Magnetic resonance imaging
myofibroblasts
Pulmonary fibrosis
Software
Statistical analysis
Stromal cells
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Summary:Fibrotic focus is a pivotal morphofunctional unit in developing fibrosis in various tissues. For most fibrotic diseases, including progressive forms, the foci are considered unable to remodel and contribute to the worsening of prognosis. Unfortunately, the dynamics of the fibrotic focus formation and resolution remains understudied. A number of data suggest that the key cell type for focus formation are activated stromal cells marked by fibroblast activated protein alpha (FAPα) due to their high capacity for extracellular matrix (ECM) remodeling. We evaluated the dynamics of fibrotic focus formation and the contribution of the main cell types, including FAPα+ cells, in this process using a murine model of bleomycin-induced lung fibrosis. We revealed the very early appearance of FAPα+ cells in lungs after injury and assumed their important involvement to the myofibroblast pool formation. During the first month after bleomycin administration, FAPα+ cells colocalize with CD206+ M2 macrophages. Interestingly, during the reversion stage, we unexpectedly observed the specific structured foci formed by CD90+FAPα+ cells, which we suggested calling “remodeling foci”. Our findings highlight the crucial role of activated stromal cells in fibrosis initiation, progression, and reversion and provide emerging issues regarding the novel targets for antifibrotic therapy.
ISSN:2073-4409
2073-4409
DOI:10.3390/cells13242064