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Science:一种能用于治疗类风湿性关节炎的蛋白Atsttrin

来源:山东大学 2011-03-15 11:19

3月10日,山东大学医学院病原生物学研究所于修平教授与美国纽约大学医学院刘传聚教授联合培养的2007级博士研究生唐伟作为第一作者的研究论文“The Growth Factor Progranulin Binds to TNF Receptors and Is Therapeutic Against Inflammatory Arthritis in Mice”被Science杂志接受。由于该研究具有重要的理论意义和应用价值而被编辑部甄选,于Science Express上先期发布。这是山东大学博士研究生第一次在Science杂志上发表研究论文。

该研究发现了生长因子progranulin(PGRN)的受体为肿瘤坏死因子受体TNFR,回答了PGRN发现20余年来的关键问题,并将PGRN与TNFα两个重要研究领域结合起来,为PGRN生物活性、炎症及自身免疫性疾病研究提供了新的思路。在此基础上,以PGRN为模板设计的工程蛋白Atsttrin(antagonist of TNF/TNFR signaling via targeting to TNF receptors)在风湿性关节炎动物模型中具有显著的治疗功效。Atsttrin对TNFR的选择性更强,具有不同于现有TNF拮抗剂的抗炎机制,显示了巨大的药物开发潜力,可能成为风湿性关节炎、克罗恩氏病、强直性脊柱炎等自身免疫性疾病的替代药物。

由于该研究潜在的临床应用价值,国内外媒体纷纷对这一研究成果进行了报道和评论。Science Daily以“Engineered Protein Has Potential for New Anti-inflammatory Treatment”为题发表评论称,科研人员构建了来源于PGRN的新型蛋白分子可能为治疗风湿性关节炎等炎症性疾病的新型治疗药物提供基础;将为风湿性关节炎、克罗恩氏病、溃疡性结肠炎、强直性脊柱炎、斑块样银屑病和银屑病性关节炎等慢性自身免疫性疾病提供替代药物。

(生物谷Bioon.com)

生物谷推荐原文出处:

Science DOI: 10.1126/science.1199214

The Growth Factor Progranulin Binds to TNF Receptors and Is Therapeutic Against Inflammatory Arthritis in Mice

Wei Tang1,2,*, Yi Lu1,2,*, Qing-Yun Tian1,*, Yan Zhang1, Feng-Jin Guo1,?, Guang-Yi Liu1, Nabeel Muzaffar Syed1, Yongjie Lai1, Edward Alan Lin1, Li Kong1, Jeffrey Su3, Fangfang Yin4,?, Ai-Hao Ding4, Alexandra Zanin-Zhorov5, Michael L. Dustin5, Jian Tao6, Joseph Craft6, Zhinan Yin7, Jian Q. Feng8, Steven B. Abramson9, Xiu-Ping Yu2, and Chuan-ju Liu1,10,§

The growth factor progranulin (PGRN) has been implicated in embryonic development, tissue repair, tumorigenesis, and inflammation, but its receptors remain unidentified. We report that PGRN bound directly to tumor necrosis factor receptors (TNFR) and disturbed the TNFα/TNFR interaction. PGRN-deficient mice were susceptible to collagen-induced arthritis, and administration of PGRN reversed inflammatory arthritis. Atsttrin, an engineered protein composed of three PGRN fragments, exhibited selective TNFR binding. PGRN and Atsttrin prevented inflammation in multiple arthritis mouse models and inhibited TNFα-activated intracellular signaling. Collectively, these findings demonstrate that PGRN is a ligand of TNFR, an antagonist of TNFα signaling and plays a critical role in the pathogenesis of inflammatory arthritis in mice. They also suggest new potential therapeutic interventions for various TNFα-mediated pathologies and conditions, including rheumatoid arthritis.

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