Fibrosis is involved in 45% of deaths in the United States, and no treatment exists to reverse the progression of the disease. Myofibroblasts are key to the progression and maintenance of fibrosis. We investigated features of cell adhesion necessary for monocytes to differentiate into myofibroblasts, seeking to identify pathways key to myofibroblast differentiation. Blocking antibodies against integrins α3, αM, and αMβ2 de-differentiate myofibroblasts in vitro, lower the pro-fibrotic secretome of myofibroblasts, and reverse lung and kidney fibrosis in vivo. Decorin’s collagen-binding peptide directs blocking antibodies (against integrins-α3, -αM, -αMβ2) to both fibrotic lungs and fibrotic kidneys, reducing the dose of antibody necessary to reverse fibrosis. This targeted immunotherapy blocking key integrins may be an effective therapeutic for the treatment and reversal of fibrosis.

中文翻译：

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阻断针对整合素-α3、-αM 和 -αMβ2 的抗体去分化肌成纤维细胞并逆转肺和肾纤维化

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。肌成纤维细胞是纤维化进展和维持的关键。我们研究了单核细胞分化成肌成纤维细胞所必需的细胞粘附特征，试图确定肌成纤维细胞分化的关键途径。在体外阻断针对整合素 α3、αM 和 αMβ2 的抗体去分化肌成纤维细胞，降低肌成纤维细胞的促纤维化分泌组，并在体内逆转肺和肾纤维化. 核心蛋白聚糖的胶原蛋白结合肽将阻断抗体（针对整合素-α3、-αM、-αMβ2）引导至纤维化肺和纤维化肾脏，从而减少逆转纤维化所需的抗体剂量。这种阻断关键整合素的靶向免疫疗法可能是治疗和逆转纤维化的有效疗法。