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bioRxiv · 10.1101/2021.06.07.447403

Myofibroblast differentiation is governed by adhesion mechanics, and inhibition of the stress sensor Talin2 reverses lung fibrosis

WHITE, M. J. V.·Ozkan, M.·Medellin, J. E. G.·Hubbell, J.
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Abstract

Fibrosis is involved in 45% of deaths in the United States, and no treatment exists to reverse progression of the disease. In order 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 morphology, -smooth muscle actin content, collagen I content, and lowers the pro-fibrotic secretome of myofibroblasts. We find that knockdown of talin2 de-differentiates myofibroblasts, talin2 knockdown reverses bleomycin-induced lung fibrosis in mice, and Tln2 -/-mice are resistant to unilateral ureteral obstruction-induced kidney fibrosis and are resistant to bleomycin-induced lung fibrosis. Talin2 inhibition is a potential treatment for reversing lung and kidney fibroses. One Sentence SummarySilencing the stress sensor Talin2 reverses myofibroblast differentiation and existing fibrosis.

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WHITE, M. J. V., Ozkan, M., Medellin, J. E. G., Hubbell, J.. 2021-06-07. Myofibroblast differentiation is governed by adhesion mechanics, and inhibition of the stress sensor Talin2 reverses lung fibrosis. https://doi.org/10.1101/2021.06.07.447403

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