治疗性抑制 JAK-STAT 通路以治疗炎症性肠病。

IF 9.3 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Cytokine & Growth Factor Reviews Pub Date : 2024-08-03 DOI:10.1016/j.cytogfr.2024.07.008
Zihan Chen , Ping Jiang , Dan Su , Yu Zhao , Mingming Zhang
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引用次数: 0

摘要

炎症性肠病(IBD)包括一组病因不明的非特异性慢性肠道炎症。目前的治疗和长期管理主要涉及生物制剂。然而,一些患者会出现治疗失败或对生物制剂不耐受的情况[1],这使得这些患者成为 IBD 研究的重点。Janus 激酶(JAK)-信号转导和转录激活因子(STAT)信号转导通路对免疫和炎症反应的调控至关重要[2],在 IBD 的发病机制中发挥着重要作用。JAK 抑制剂通过抑制 JAK-STAT 信号转导通路的传递来缓解 IBD。作为首个治疗 IBD 的小分子口服抑制剂,JAK 抑制剂极大地改善了 IBD 的治疗,并取得了显著疗效,其中托法替尼和乌达替尼已被批准用于治疗溃疡性结肠炎(UC)[3]。JAK 抑制剂可有效缓解生物制剂治疗失败的 IBD 患者的肠道炎症,这可能为难治性 IBD 患者带来新的治疗机会。本综述旨在阐明 JAK-STAT 信号转导通路在 IBD 发病机制中的关键作用,研究其在 IBD 不同细胞类型中的作用,并探讨 JAK 抑制剂作为治疗药物的研究进展,为新的 IBD 治疗策略铺平道路。
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Therapeutic inhibition of the JAK-STAT pathway in the treatment of inflammatory bowel disease

Inflammatory bowel disease (IBD) encompasses a group of non-specific chronic intestinal inflammatory conditions of unclear etiology. The current treatment and long-term management primarily involve biologics. Nevertheless, some patients experience treatment failure or intolerance to biologics [1], making these patients a primary focus of IBD research. The Janus kinase (JAK)-Signal Transducers and Activator of Transcription (STAT) signal transduction pathway is crucial to the regulation of immune and inflammatory responses [2], and plays an important role in the pathogenesis of IBD. JAK inhibitors alleviate IBD by suppressing the transmission of JAK-STAT signaling pathway. As the first small-molecule oral inhibitor for IBD, JAK inhibitors greatly improved the treatment of IBD and have demonstrated significant efficacy, with tofacitinib and upadacitinib being approved for the treatment of ulcerative colitis (UC) [3]. JAK inhibitors can effectively alleviate intestinal inflammation in IBD patients who have failed to receive biologics, which may bring new treatment opportunities for refractory IBD patients. This review aims to elucidate the crucial roles of JAK-STAT signal transduction pathway in IBD pathogenesis, examine its role in various cell types within IBD, and explore the research progress of JAK inhibitors as therapeutic agents, paving the road for new IBD treatment strategies.

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来源期刊
Cytokine & Growth Factor Reviews
Cytokine & Growth Factor Reviews 生物-生化与分子生物学
CiteScore
21.10
自引率
1.50%
发文量
61
审稿时长
22 days
期刊介绍: Cytokine & Growth Factor Reviews is a leading publication that focuses on the dynamic fields of growth factor and cytokine research. Our journal offers a platform for authors to disseminate thought-provoking articles such as critical reviews, state-of-the-art reviews, letters to the editor, and meeting reviews. We aim to cover important breakthroughs in these rapidly evolving areas, providing valuable insights into the multidisciplinary significance of cytokines and growth factors. Our journal spans various domains including signal transduction, cell growth and differentiation, embryonic development, immunology, tumorigenesis, and clinical medicine. By publishing cutting-edge research and analysis, we aim to influence the way researchers and experts perceive and understand growth factors and cytokines. We encourage novel expressions of ideas and innovative approaches to organizing content, fostering a stimulating environment for knowledge exchange and scientific advancement.
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