Therapeutic Effects of NK-HDAC-1, a Novel Histone Deacetylase Inhibitor, on Collagen-Induced Arthritis Through the Induction of Apoptosis of Fibroblast-Like Synoviocytes
Therapeutic Effects of NK-HDAC-1, a Novel Histone Deacetylase Inhibitor, on Collagen-Induced Arthritis Through the Induction of Apoptosis of Fibroblast-Like Synoviocytes
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NK-HDAC-1（一种新型组蛋白脱乙酰酶抑制剂）通过诱导成纤维样滑膜细胞凋亡对胶原诱导的关节炎的治疗作用
DOI：
10.1007/s10753-013-9616-0
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发表时间：
2013-04
期刊：
影响因子：
5.1
通讯作者：
Jin, Jin
中科院分区：
文献类型：
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作者：
Li, Zhanguo;Liu, Xu;Sun, Xiaolin;Wang, Zhenhua;Guo, Weikang;Hu, Fanlei;Yao, Haihong;Cao, Xuefeng;Jin, Jin
本研究的目的是研究新型组蛋白脱乙酰酶抑制剂 (HDACi) NK-HDAC-1 对类风湿性关节炎 (RA) 患者的胶原诱导性关节炎 (CIA) 和致病性成纤维细胞样滑膜细胞 (FLS) 的治疗效果。通过流式细胞术和荧光染色评估用NK-HDAC-1处理的FLS的增殖和凋亡。通过 ELISA 测定 NK-HDAC-1 治疗对促炎细胞因子产生的影响。在 DBA/1 小鼠中建立 CIA，并在关节炎发作后每天施用 NK-HDAC-1 或载体。计算临床和组织学评分以评估 NK-HDAC-1 的治疗效果。 NK-HDAC-1 通过细胞周期阻滞在 G2/M 检查点并增强 FLS 的凋亡来显着抑制 FLS 的增殖。 NK-HDAC-1 处理期间半胱天冬酶的活性增加。 FLS 产生的 IL-6 也被 NK-HDAC-1 抑制。此外，口服NK-HDAC-1可显着增强体内滑膜细胞凋亡并抑制CIA进展。与表现出中等预防效果的次丙烯酰苯胺异羟肟酸相比，NK-HDAC-1在CIA中表现出治疗效果。 NK-HDAC-1 是一种新型 HDACi，可以通过调节 FLS 的激活、凋亡和炎症反应来改善炎症性关节炎。这是第一项支持 NK-HDAC-1 可能是 RA 潜在治疗剂的研究。
The purpose of this study is to investigate the therapeutic effects of a novel histone deacetylase inhibitor (HDACi), NK-HDAC-1, on collagen-induced arthritis (CIA) and pathogenic fibroblast-like synoviocytes (FLSs) from patients with rheumatoid arthritis (RA). The proliferation and apoptosis of FLSs treated with NK-HDAC-1 were evaluated by flow cytometry and fluorescence staining. The effect of NK-HDAC-1 treatment on pro-inflammatory cytokine production was determined by ELISA. CIA was established in DBA/1 mice, and NK-HDAC-1 or vehicle was administered daily after the onset of arthritis. Clinical and histological scores were calculated to assess the therapeutic efficacy of NK-HDAC-1. NK-HDAC-1 significantly inhibited the proliferation of FLSs through cell cycle arrest at the G2/M checkpoint and enhanced apoptosis of FLSs. The activity of caspases was increased during NK-HDAC-1 treatment. IL-6 production by FLSs was also suppressed by NK-HDAC-1. Furthermore, the oral administration of NK-HDAC-1 significantly enhanced synoviocyte apoptosisin vivoand inhibited CIA progression. Compared with subcroylanilide hydroxamic acid which exhibited moderate prophylactic efficacy, NK-HDAC-1 demonstrated therapeutic efficacy in CIA. NK-HDAC-1 is a novel HDACi that may ameliorate inflammatory arthritis by regulating the activation, apoptosis, and inflammatory responses of FLSs. This is the first study to support that NK-HDAC-1 may be a potential therapeutic agent for RA.
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影响因子：
--
作者：
Nishikawa, M;Myoui, A;Yoshikawa, H
通讯作者：
Yoshikawa, H
影响因子：
11.2
作者：
Karthikeyan Kandasamy;S. Srinivasula;E. Alnemri;C. Thompson;S. Korsmeyer;J. Bryant;R. K Srivastava
通讯作者：
Karthikeyan Kandasamy;S. Srinivasula;E. Alnemri;C. Thompson;S. Korsmeyer;J. Bryant;R. K Srivastava
影响因子：
7.3
作者：
Lin, H-S;Hu, C-Y;Clement-Lacroix, P.
通讯作者：
Clement-Lacroix, P.
NK-HDAC-1 的发现和广泛的体外评估：作为一种有前景的先导物的手性组蛋白脱乙酰酶抑制剂
影响因子：
7.3
作者：
Hou, Jingli;Li, Zhonghua;Wang, Peng George
通讯作者：
Wang, Peng George
影响因子：
82.9
作者：
通讯作者：
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