Progranulin: a promising therapeutic target for rheumatoid arthritis.

Progranulin: a promising therapeutic target for rheumatoid arthritis.
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DOI:
10.1016/j.febslet.2011.04.065
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发表时间:
2011-12-01
期刊:
影响因子:
3.5
通讯作者:
Liu CJ
Liu CJ
中科院分区:
生物学3区
文献类型:
--
作者:
Liu CJ

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颗粒蛋白前体(PGRN)是一种具有多种功能的自分泌生长因子。本文综述了PGRN与软骨和关节炎中细胞外基质蛋白、蛋白水解酶、炎性细胞因子和细胞表面受体的相互作用,特别关注PGRN与TNF受体(TNFR)之间的相互作用及其在炎症性关节炎中的意义。该论文还强调了Atsttrin,这是一种由三个PGRN片段组成的工程蛋白质,可预防几种炎症性关节炎模型中的炎症。PGRN作为TNFR配体和TNF α信号传导拮抗剂的鉴定,以及Atsttrin的发现,不仅加深了我们对关节炎发病机制的理解,而且为各种TNF α介导的病理和病症(包括类风湿性关节炎)提供了新的治疗干预。
Progranulin (PGRN) is an autocrine growth factor with multiple functions. This review provides updates about the interplays of PGRN with extracellular matrix proteins, proteolytic enzymes, inflammatory cytokines, and cell surface receptors in cartilage and arthritis, with a special focus on the interaction between PGRN and TNF receptors (TNFR) and its implications in inflammatory arthritis. The paper also highlights Atsttrin, an engineered protein composed of three PGRN fragments that prevents inflammation in several inflammatory arthritis models. Identification of PGRN as a ligand of TNFR and an antagonist of TNFα signaling, together with the discovery of Atsttrin, not only betters our understanding of the pathogenesis of arthritis, but also provides new therapeutic interventions for various TNFα-mediated pathologies and conditions, including rheumatoid arthritis.
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