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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| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
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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| Summary: | 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. |
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| ISSN: | 2045-2322 |