10-Hydroxy-2-decenoic acid inhibiting the proliferation of fibroblast-like synoviocytes by PI3K-AKT pathway.

10-Hydroxy-2-decenoic acid inhibiting the proliferation of fibroblast-like synoviocytes by PI3K-AKT pathway.
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10-羟基-2-癸烯酸通过 PI3K-AKT 通路抑制成纤维样滑膜细胞增殖

DOI:
10.1016/j.intimp.2015.05.036
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发表时间:
2015-09
期刊:
International Immunopharmacology(JCR3区)
影响因子:
--
通讯作者:
Yang, Xinyu
Yang, Xinyu
中科院分区:
其他
文献类型:
--
作者:
Chuka, Chifundo Martha;Ge, Renshan;Zhao, Shujiang;Yang, Xinyu

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探讨10 H2 DA抑制类风湿关节炎患者滑膜成纤维细胞增殖的机制。MTT法、HDAC活性比色法和Western-blot法检测10 H2 DA对FLS细胞增殖、HDAC活性和组蛋白乙酰化水平的影响。原代培养RA患者FLS细胞中的不同基因,并用10 H2 DA处理。然后通过Human Transcriptome 1.0 ST微阵列对其进行筛选,并通过实时PCR进行验证。结果表明,10 H2 DA处理的FLS细胞活力和HDAC活性呈剂量依赖性和时间依赖性下降,同时H3和H4的乙酰化呈时间依赖性诱导。用HTA 1.0鉴定了697个不同的基因。实时荧光定量PCR证实PI 3 K-AKT通路的7个靶基因表达下调,4个靶基因表达上调。提示10 H2 DA是一种潜在的HDACI,通过PI 3 K-AKT途径抑制FLS细胞增殖。
To reveal the mechanism of 10H2DA inhibiting the proliferation of fibroblast-like synoviocytes (FLSs) of RA patients. Cell proliferation, HDAC activity and histone acetylation level of FLS cells treated with 10H2DA were detected by MTT assay, Colorimetric HDAC Activity Assay and Western-blot. Different genes in FLS cells from RA patients were primary cultured and treated with 10H2DA. They were then screened by Human Transcriptome 1.0 ST microarrays and verified by real-time PCR. The results showed dose-dependent and time-dependent decreases in cell viability and HDAC activity in FLSs treated with 10H2DA, and time-dependent induction in the acetylation of H3 and H4 at the same time. 697 different genes were identified by HTA 1.0. The expressions of 7 target genes of the PI3K–AKT pathway were decreased and 4 target genes of cytokine-cytokine receptor interaction were increased verified by real-time PCR. These results imply that 10H2DA is a potential HDACI which inhibits the proliferation of FLS cells by PI3K–AKT pathway.
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