Transcriptional regulation of collagenase (MMP-1, MMP-13) genes in arthritis: integration of complex signaling pathways for the recruitment of gene-specific transcription factors.

Transcriptional regulation of collagenase (MMP-1, MMP-13) genes in arthritis: integration of complex signaling pathways for the recruitment of gene-specific transcription factors.
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DOI:
10.1186/ar401
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发表时间:
2002
期刊:
Arthritis research
影响因子:
--
通讯作者:
Brinckerhoff CE
Brinckerhoff CE
中科院分区:
其他
文献类型:
--
作者:
Vincenti MP;Brinckerhoff CE

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基质金属蛋白酶(MMP)-1、MMP-8和MMP-13是降解软骨中的II型胶原的间质胶原酶;这是类风湿性关节炎和骨关节炎进展中的关键步骤。在这些酶中,MMP-1和MMP-13的表达响应于IL-1和肿瘤坏死因子-α而显著增加,并且在关节炎组织中观察到这些胶原酶的水平升高。因此,苦参碱介导的MMP-1和MMP-13基因调控是关节炎研究的重要课题。在这篇综述中,我们讨论了目前的MMP-1和MMP-13的转录调控模型,重点是信号中间体和转录因子,可能是未来的新的关节炎药物的发展目标。
Matrix metalloproteinase (MMP)-1, MMP-8 and MMP-13 are interstitial collagenases that degrade type II collagen in cartilage; this is a committed step in the progression of rheumatoid arthritis and osteoarthritis. Of these enzymes, the expression of MMP-1 and MMP-13 is substantially increased in response to IL-1 and tumor necrosis factor-α, and elevated levels of these collagenases are observed in arthritic tissues. Therefore, cytokine-mediated MMP-1 and MMP-13 gene regulation is an important issue in arthritis research. In this review, we discuss current models of MMP-1 and MMP-13 transcriptional regulation, with a focus on signaling intermediates and transcription factors that may be future targets for the development of new arthritis drugs.
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