肌成纤维细胞
纤维化
整合素
阻断抗体
免疫疗法
医学
抗体
癌症研究
病理
肺
免疫学
受体
免疫系统
内科学
作者
Michael J. V. White,melis ozkan,Michal M. Raczy,Jorge Emiliano Gomez Medellin,Kyle M Koss,Aaron T. Alpar,Bilal A. Naved,Jason A. Wertheim,Jeffrey A. Hubbell
标识
DOI:10.1101/2021.06.07.447405
摘要
Abstract 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. Summary Blocking antibodies against integrins-α3, -αM, and -αMβ2 can be targeted to sites of fibrosis, reverse lung and kidney fibroses, and offer the potential to bring immunotherapy to fibrosis
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