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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2024-12-01
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| author | Nataliya Andreevna Basalova Maksim Alexandrovich Vigovskiy Vladimir Sergeevich Popov Evgeniya Alexandrovna Lagereva Olga Alexandrovna Grigorieva Anastasia Yuryevna Efimenko |
| author_facet | Nataliya Andreevna Basalova Maksim Alexandrovich Vigovskiy Vladimir Sergeevich Popov Evgeniya Alexandrovna Lagereva Olga Alexandrovna Grigorieva Anastasia Yuryevna Efimenko |
| author_sort | Nataliya Andreevna Basalova |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-292d031039724c05a7511d996816f5da |
| institution | Kabale University |
| issn | 2073-4409 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | MDPI AG |
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| series | Cells |
| spelling | doaj-art-292d031039724c05a7511d996816f5da2024-12-27T14:16:29ZengMDPI AGCells2073-44092024-12-011324206410.3390/cells13242064The Role of Activated Stromal Cells in Fibrotic Foci Formation and ReversionNataliya Andreevna Basalova0Maksim Alexandrovich Vigovskiy1Vladimir Sergeevich Popov2Evgeniya Alexandrovna Lagereva3Olga Alexandrovna Grigorieva4Anastasia Yuryevna Efimenko5Centre for Regenerative Medicine, Medical Research and Educational Institute, Lomonosov Moscow State University, 119192 Moscow, RussiaCentre for Regenerative Medicine, Medical Research and Educational Institute, Lomonosov Moscow State University, 119192 Moscow, RussiaCentre for Regenerative Medicine, Medical Research and Educational Institute, Lomonosov Moscow State University, 119192 Moscow, RussiaCentre for Regenerative Medicine, Medical Research and Educational Institute, Lomonosov Moscow State University, 119192 Moscow, RussiaCentre for Regenerative Medicine, Medical Research and Educational Institute, Lomonosov Moscow State University, 119192 Moscow, RussiaCentre for Regenerative Medicine, Medical Research and Educational Institute, Lomonosov Moscow State University, 119192 Moscow, RussiaFibrotic 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.https://www.mdpi.com/2073-4409/13/24/2064activated stromal cellsfibrosismyofibroblastsfibroblast activation proteinFAPαCD90 (THY-1) |
| spellingShingle | Nataliya Andreevna Basalova Maksim Alexandrovich Vigovskiy Vladimir Sergeevich Popov Evgeniya Alexandrovna Lagereva Olga Alexandrovna Grigorieva Anastasia Yuryevna Efimenko The Role of Activated Stromal Cells in Fibrotic Foci Formation and Reversion Cells activated stromal cells fibrosis myofibroblasts fibroblast activation protein FAPα CD90 (THY-1) |
| title | The Role of Activated Stromal Cells in Fibrotic Foci Formation and Reversion |
| title_full | The Role of Activated Stromal Cells in Fibrotic Foci Formation and Reversion |
| title_fullStr | The Role of Activated Stromal Cells in Fibrotic Foci Formation and Reversion |
| title_full_unstemmed | The Role of Activated Stromal Cells in Fibrotic Foci Formation and Reversion |
| title_short | The Role of Activated Stromal Cells in Fibrotic Foci Formation and Reversion |
| title_sort | role of activated stromal cells in fibrotic foci formation and reversion |
| topic | activated stromal cells fibrosis myofibroblasts fibroblast activation protein FAPα CD90 (THY-1) |
| url | https://www.mdpi.com/2073-4409/13/24/2064 |
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