Mithramycin has inhibitory effects on gliostatin and matrix metalloproteinase expression induced by gliostatin in rheumatoid fibroblast-like synoviocytes.
Mithramycin has inhibitory effects on gliostatin and matrix metalloproteinase expression induced by gliostatin in rheumatoid fibroblast-like synoviocytes.
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Mithramycin 对类风湿成纤维细胞样滑膜细胞中的胶质抑素和由胶质抑素诱导的基质金属蛋白酶表达具有抑制作用。
DOI：
10.1080/14397595.2017.1350332
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Otsuka T.
中科院分区：
文献类型：
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作者：
Tatematsu N;Waguri-Nagaya Y;Kawaguchi Y;Oguri Y;Ikuta K;Kobayashi M;Nozaki M;Asai K;Aoyama M;Otsuka T.
目的：葡萄糖抑素(Gliostatin，GLS)具有促血管和致关节炎活性，并具有类似胸苷磷酸化酶的酶活性。在类风湿关节炎(RA)患者的滑膜中观察到GLS的异常产生。基质金属蛋白酶(MMPs)参与关节破坏。GLS和一些MMP基因的启动子含有Sp1结合位点。我们检测了Sp1抑制剂米曲霉素对GLS诱导的成纤维样滑膜细胞(FLSS)表达GLS和MMPs的抑制作用。米曲霉素预处理的FLSS与GLS共同培养。用逆转录聚合酶链式反应检测GLS和MMP1、MMP2、MMP3、MMP9、MMP13mRNA的表达水平。结果：GLS可显著上调GLS自身及MMP1、MMP3、MMP9、MMP13的表达，米曲霉素组这种作用明显减弱。结论：米曲霉素可下调GLS诱导的FLSS中GLS和MMP1、MMP3、MMP9、MMP13的表达。由于GLS在RA中起着病理作用，使用米曲霉素等药物阻断GLS的刺激可能是一种新的抗风湿治疗方法。
Objectives:Gliostatin (GLS) has angiogenic and arthritogenic activities and enzymatic activity as thymidine phosphorylase. Aberrant GLS production has been observed in the synovial membranes of patients with rheumatoid arthritis (RA). Matrix metalloproteinases (MMPs) are involved in joint destruction. Promoters ofGLSand someMMPgenes contain Sp1 binding sites. We examined the inhibitory effect of the Sp1 inhibitor mithramycin on GLS-induced GLS and MMP expression in cultured fibroblast-like synoviocytes (FLSs).Methods:Synovial tissue samples were obtained from patients with RA. FLSs pretreated with mithramycin were cultured with GLS. The mRNA expression levels of GLS and MMP-1, MMP-2, MMP-3, MMP-9, and MMP-13 were determined using reverse transcription polymerase chain reactions. Protein levels were measured using enzyme immunoassay and gelatin zymography.Results:GLS upregulated the expression of GLS itself and of MMP-1, MMP-3, MMP-9, and MMP-13, an effect significantly reduced by treatment with mithramycin. GLS and mithramycin had no effect on MMP-2 expression.Conclusions:Mithramycin downregulated the increased expression of GLS and MMP-1, MMP-3, MMP-9, and MMP-13 in FLSs treated with GLS. Because GLS plays a pathological role in RA, blocking GLS stimulation using an agent such as mithramycin may be a novel approach to antirheumatic therapy.