Antifibrotic therapy in scleroderma: Extracellular or intracellular targeting of activated fibroblasts?

Antifibrotic therapy in scleroderma: Extracellular or intracellular targeting of activated fibroblasts?
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硬皮病的抗纤维化治疗:细胞外或细胞内靶向活化的成纤维细胞?

DOI:
10.1007/s11926-004-0062-8
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发表时间:
2004
影响因子:
5
通讯作者:
J. Varga
J. Varga
中科院分区:
医学2区
文献类型:
--
作者:
J. Varga

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治疗抗细胞因子的方法使慢性炎症性疾病的治疗发生了革命性的变化,转化生长因子-β(转化生长因子-β)是纤维化发病机制中的关键因素,目前正在对硬皮病的治疗进行评估。一些考虑因素决定了对抗转化生长因子-β干预采取谨慎的方法。这些包括多种细胞因子在纤维化发病机制中重叠作用的可能性,以及考虑到转化生长因子-β具有众多的体内平衡功能,阻断转化生长因子-hGMP可能会产生严重的不良后果。此外,硬皮病成纤维细胞作为自主激活的细胞,可能对阻断转化生长因子-β信号没有反应。本文回顾了这些担忧背后的实验证据,并指出了解决和克服这些担忧的合理方法。
Therapeutic anticytokine approaches have revolutionized the treatment of chronic inflammatory diseases, and targeting of transforming growth factor-beta (TGF-β), a key factor in the pathogenesis of fibrosis, is undergoing evaluation for scleroderma. Several considerations dictate a cautious approach to anti-TGF-β interventions. These include the possibility of multiple cytokines having overlapping roles in the pathogenesis of fibrosis and concerns that, in light of its numerous homeostatic functions, blocking TGF-β may have serious adverse consequences. Furthermore, as autonomously activated cells, scleroderma fibroblasts may be unresponsive to blockade of TGF-β signaling. This article reviews the experimental evidence underlying these concerns, and indicates rational approaches to addressing and overcoming them.
DOI: 10.1073/pnas.92.10.4254
发表时间: 1995-05-09
影响因子: 11.1
作者:
PIERCE, DF;GORSKA, AE;MOSES, HL
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发表时间: 2002
期刊: Frontiers in bioscience : a journal and virtual library.
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