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, α-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.

中文翻译：

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肌成纤维细胞分化受粘附力学控制，抑制 Talin2 可逆转肺和肾纤维化

在美国，45% 的死亡与纤维化有关，并且不存在逆转疾病进展的治疗方法。为了找到纤维化治疗的新靶点，我们开发了一个单核细胞分化为肌成纤维细胞的模型，使我们能够筛选参与肌成纤维细胞分化的蛋白质。抑制由我们的模型 talin2 生成的新蛋白质靶标，可降低肌成纤维细胞形态、α-平滑肌肌动蛋白含量、胶原蛋白 I 含量，并降低肌成纤维细胞的促纤维化分泌组。我们发现 talin2 的敲低使肌成纤维细胞去分化，talin2 的敲低逆转了博莱霉素诱导的小鼠肺纤维化，而 Tln2 -/- 小鼠对单侧输尿管梗阻诱导的肾纤维化具有抗性，并且对博来霉素诱导的肺纤维化具有抗性。