Inhibition of Talin2 dedifferentiates myofibroblasts and reverses lung and kidney fibrosis
Abstract Fibrosis is involved in 45% of deaths in the United States, and no treatment exists to reverse progression of the disease. To find novel targets for fibrosis therapeutics, we developed a model for the differentiation of monocytes to myofibroblasts that allowed us to screen for proteins invo...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-05-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-025-00939-x |
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| author | Michael J. V. White Melis Ozkan Jorge Emiliano Gomez Medellin Ani Solanki Jeffrey A. Hubbell |
| author_facet | Michael J. V. White Melis Ozkan Jorge Emiliano Gomez Medellin Ani Solanki Jeffrey A. Hubbell |
| author_sort | Michael J. V. White |
| collection | DOAJ |
| description | Abstract Fibrosis is involved in 45% of deaths in the United States, and no treatment exists to reverse progression of the disease. To find novel targets for fibrosis therapeutics, we developed a model for the differentiation of monocytes to myofibroblasts that allowed us to screen for proteins involved in myofibroblast differentiation. Inhibition of a novel protein target generated by our model, talin2, reduces myofibroblast-specific morphology, α-smooth muscle actin content, and collagen I content and lowers the pro-fibrotic secretome of myofibroblasts. We find that knockdown of talin2 de-differentiates myofibroblasts and reverses bleomycin-induced lung fibrosis in mice, and further that Tln2 −/− mice are resistant to bleomycin-induced lung fibrosis and resistant to unilateral ureteral obstruction-induced kidney fibrosis. Talin2 inhibition is thus a potential treatment for reversing lung and kidney fibroses. |
| format | Article |
| id | doaj-art-e090b119e16e4017b178587accc6c843 |
| institution | OA Journals |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-e090b119e16e4017b178587accc6c8432025-08-20T01:53:11ZengNature PortfolioScientific Reports2045-23222025-05-0115111910.1038/s41598-025-00939-xInhibition of Talin2 dedifferentiates myofibroblasts and reverses lung and kidney fibrosisMichael J. V. White0Melis Ozkan1Jorge Emiliano Gomez Medellin2Ani Solanki3Jeffrey A. Hubbell4Pritzker School of Molecular Engineering, University of ChicagoPritzker School of Molecular Engineering, University of ChicagoPritzker School of Molecular Engineering, University of ChicagoAnimal Resources Center, University of ChicagoPritzker School of Molecular Engineering, University of ChicagoAbstract Fibrosis is involved in 45% of deaths in the United States, and no treatment exists to reverse progression of the disease. To find novel targets for fibrosis therapeutics, we developed a model for the differentiation of monocytes to myofibroblasts that allowed us to screen for proteins involved in myofibroblast differentiation. Inhibition of a novel protein target generated by our model, talin2, reduces myofibroblast-specific morphology, α-smooth muscle actin content, and collagen I content and lowers the pro-fibrotic secretome of myofibroblasts. We find that knockdown of talin2 de-differentiates myofibroblasts and reverses bleomycin-induced lung fibrosis in mice, and further that Tln2 −/− mice are resistant to bleomycin-induced lung fibrosis and resistant to unilateral ureteral obstruction-induced kidney fibrosis. Talin2 inhibition is thus a potential treatment for reversing lung and kidney fibroses.https://doi.org/10.1038/s41598-025-00939-x |
| spellingShingle | Michael J. V. White Melis Ozkan Jorge Emiliano Gomez Medellin Ani Solanki Jeffrey A. Hubbell Inhibition of Talin2 dedifferentiates myofibroblasts and reverses lung and kidney fibrosis Scientific Reports |
| title | Inhibition of Talin2 dedifferentiates myofibroblasts and reverses lung and kidney fibrosis |
| title_full | Inhibition of Talin2 dedifferentiates myofibroblasts and reverses lung and kidney fibrosis |
| title_fullStr | Inhibition of Talin2 dedifferentiates myofibroblasts and reverses lung and kidney fibrosis |
| title_full_unstemmed | Inhibition of Talin2 dedifferentiates myofibroblasts and reverses lung and kidney fibrosis |
| title_short | Inhibition of Talin2 dedifferentiates myofibroblasts and reverses lung and kidney fibrosis |
| title_sort | inhibition of talin2 dedifferentiates myofibroblasts and reverses lung and kidney fibrosis |
| url | https://doi.org/10.1038/s41598-025-00939-x |
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