White Michael J V, Ozkan Melis, Gomez-Medellin Jorge Emiliano, Rączy Michal M, Koss Kyle M, Solanki Ani, Zhang Zheng Jenny, Alpar Aaron T, Naved Bilal A, Wertheim Jason, Hubbell Jeffrey A
Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL, 60637, USA.
Committee on Immunology, University of Chicago, Chicago, IL, 60637, USA.
Sci Rep. 2024 Sep 16;14(1):21623. doi: 10.1038/s41598-024-70737-4.
Fibrosis is involved in 45% of deaths in the United States, and no treatment exists to reverse the progression of lung or kidney fibrosis. 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 treat lung fibrosis and inhibit kidney fibrosis in vivo. Decorin's collagen-binding peptide can be used to direct functionalized blocking antibodies (against integrins-α3, -αM, -αMβ2) to both fibrotic lungs and fibrotic kidneys, reducing the dose of antibody necessary to treat fibrosis. This targeted immunotherapy blocking key integrins may be an effective therapeutic for the treatment of fibrosis.
在美国，45%的死亡病例都与纤维化有关，目前尚无治疗方法能够逆转肺纤维化或肾纤维化的进程。肌成纤维细胞是纤维化进展和维持的关键因素。我们研究了单核细胞分化为肌成纤维细胞所需的细胞黏附特征，旨在确定肌成纤维细胞分化的关键途径。针对整合素α3、αM和αMβ2的阻断抗体可使体外培养的肌成纤维细胞去分化，降低肌成纤维细胞的促纤维化分泌组，并在体内治疗肺纤维化和抑制肾纤维化。核心蛋白聚糖的胶原结合肽可用于将功能化阻断抗体（针对整合素-α3、-αM、-αMβ2）导向纤维化的肺和肾，减少治疗纤维化所需的抗体剂量。这种靶向免疫疗法通过阻断关键整合素，可能成为治疗纤维化的有效疗法。
