p38 MAPK通路在类风湿关节炎中的作用:侧面观察。

Q4 Medicine
Open Rheumatology Journal Pub Date : 2012-01-01 Epub Date: 2012-09-07 DOI:10.2174/1874312901206010209
Andrew R Clark, Jonathan LE Dean
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引用次数: 85

摘要

p38丝裂原活化蛋白激酶(MAPK)信号通路与类风湿关节炎(RA)病理基础的许多过程密切相关。多年来,它一直被认为是开发新的抗炎药物的有希望的目标,用于治疗RA和其他慢性免疫介导的炎症性疾病。然而,最近几项临床试验的结果令人失望。如果p38 MAPK明显有助于炎症介质的过度产生,破坏骨和软骨,为什么会这样呢?我们认为,为了解释p38抑制剂在风湿病临床中的明显失败,我们需要更好地理解p38通路的复杂性及其与其他细胞信号通路的多层次通信。在这篇综述中,我们从一个稍微不同的角度来看待p38 MAPK途径,强调其在基因表达的转录后而不是转录控制中的作用,以及它对炎症反应的非期而非期的贡献。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

The p38 MAPK Pathway in Rheumatoid Arthritis: A Sideways Look.

The p38 MAPK Pathway in Rheumatoid Arthritis: A Sideways Look.

The p38 MAPK Pathway in Rheumatoid Arthritis: A Sideways Look.

The p38 MAPK Pathway in Rheumatoid Arthritis: A Sideways Look.

The p38 mitogen-activated protein kinase (MAPK) signaling pathway has been strongly implicated in many of the processes that underlie the pathology of rheumatoid arthritis (RA). For many years it has been considered a promising target for development of new anti-inflammatory drugs with which to treat RA and other chronic immune-mediated inflammatory diseases. However, several recent clinical trials have concluded in a disappointing manner. Why is this so, if p38 MAPK clearly contributes to the excessive production of inflammatory mediators, the destruction of bone and cartilage? We argue that, to explain the apparent failure of p38 inhibitors in the rheumatology clinic, we need to understand better the complexities of the p38 pathway and its many levels of communication with other cellular signaling pathways. In this review we look at the p38 MAPK pathway from a slightly different perspective, emphasising its role in post-transcriptional rather than transcriptional control of gene expression, and its contribution to the off-phase rather than the on-phase of the inflammatory response.

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来源期刊
Open Rheumatology Journal
Open Rheumatology Journal Medicine-Rheumatology
CiteScore
0.80
自引率
0.00%
发文量
2
期刊介绍: ENTHAM Open publishes a number of peer-reviewed, open access journals. These free-to-view online journals cover all major disciplines of science, medicine, technology and social sciences. BENTHAM Open provides researchers a platform to rapidly publish their research in a good-quality peer-reviewed journal. All peer-reviewed accepted submissions meeting high research and ethical standards are published with free access to all.
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