The role of histone deacetylases in rheumatoid arthritis fibroblast-like synoviocytes
The role of histone deacetylases in rheumatoid arthritis fibroblast-like synoviocytes
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DOI：
10.1042/bst20130053
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发表时间：
2013-06-01
影响因子：
3.9
通讯作者：
Wilson, Anthony G.
中科院分区：
文献类型：
--
作者：
Hawtree, Sarah;Muthana, Munitta;Wilson, Anthony G.
类风湿性关节炎（RA）是一种滑膜关节炎性疾病，影响约1%的人口。参与RA关节组织损伤的主要细胞类型之一是FLS（成纤维细胞样滑膜细胞）。这些具有半转化的、自身侵袭性表型，其典型表现为接触抑制的丧失、细胞凋亡减少和基质降解酶的产生。这种表型的发展机制尚不清楚，然而，越来越多的证据表明，在基因表达的表观遗传调控的改变。组蛋白尾部氨基酸乙酰化的减少是一种与转录抑制相关的表观遗传标记，受组蛋白去乙酰化酶（HDAC）家族控制。迄今为止，已有证据表明HDAC参与了FLS的自身侵袭表型，并且向RA动物模型和青少年关节炎个体施用HDAC抑制剂已显示出减轻炎症和组织损伤的功效。这突出了HDAC在疾病发病机制中的作用，更重要的是，HDAC是潜在的新型治疗靶点。
RA (rheumatoid arthritis) is an inflammatory disease of synovial joints affecting approximately 1% of the population. One of the main cell types involved in damage to RA joint tissue is the FLSs (fibroblast-like synoviocytes). These have a semi-transformed, auto-aggressive phenotype typified by loss of contact inhibition, reduced apoptosis and the production of matrix-degrading enzymes. The mechanisms involved in the development of this phenotype are unclear; however, increasing evidence implicates alterations in the epigenetic regulation of gene expression. Reduced acetylation of amino acids in the tails of histone proteins is an epigenetic mark associated with transcriptional repression and is controlled by the HDAC (histone deacetylase) enzyme family. To date, evidence has implicated HDACs in the auto-aggressive phenotype of FLSs, and administration of HDAC inhibitors to both animal models of RA and individuals with juvenile arthritis has shown efficacy in attenuating inflammation and tissue damage. This highlights a role for HDACs in disease pathogenesis and, more importantly, that HDACs are potential novel therapeutic targets.