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

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. We assessed these screening results for proteins to target for novel fibrosis therapeutics. Here we test whether inhibition of a novel protein target generated by our model, talin2, can prevent and even reverse myofibroblast differentiation. We find that knockdown of talin2 de-differentiates myofibroblasts, altering myofibroblast morphology, α-smooth muscle actin and collagen content, and the secretome. Talin2 inhibition reverses bleomycin-induced lung fibrosis in mice. Talin2 inhibition could be a novel treatment for reversing lung fibrosis.