Thioredoxin 1 is associated with the proliferation and apoptosis of rheumatoid arthritis fibroblast-like synoviocytes.
Thioredoxin 1 is associated with the proliferation and apoptosis of rheumatoid arthritis fibroblast-like synoviocytes.
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硫氧还蛋白1与类风湿性关节炎成纤维细胞样滑膜细胞的增殖和凋亡相关
DOI：
10.1007/s10067-017-3832-1
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发表时间：
2018-01
影响因子：
3.4
通讯作者：
Fan L
中科院分区：
文献类型：
--
作者：
Lu T;Zong M;Fan S;Lu Y;Yu S;Fan L
本研究旨在探讨硫氧还蛋白1（Trx 1）对类风湿关节炎成纤维样滑膜细胞（RA FLS）增殖和凋亡的影响及其可能机制。我们通过免疫组织化学和实时聚合酶链反应（RT-PCR）分析研究了Trx 1在RA和骨关节炎（OA）患者滑膜组织中的分布和表达。RA-FLSs被分离并在常氧（21%氧）或低氧（3%氧）浓度下培养。进行Trx 1-siRNA和Trx 1过表达构建体的转染以操纵Trx 1的表达。Western blot检测蛋白表达。阿霉素（Adriamycin，ADR）诱导细胞凋亡。LY-294002用于抑制PI 3 K-Akt。MTS（3-[4，5-dimethylthiazol-2-yl]-5-[3-carboxymethoxyphenyl]-2-[4-sulfophenyl]-2H-tetrazolium，inner salt）法检测细胞增殖，流式细胞术检测细胞凋亡。RA组织中Trx 1的mRNA和蛋白表达均高于OA组织。与常氧组相比，低氧组RA-FLS中Trx 1的表达水平和细胞增殖能力均增强。缺氧条件下，下调Trx 1表达可显著抑制FLS增殖，抑制PI 3 Kp 85、磷酸化Akt和Bcl-2的表达，但可显著增加FLS凋亡和活性Caspase 3和Bax的表达。常氧条件下，Trx 1过表达促进FLS增殖，促进FLS中PI 3 Kp 85、磷酸化Akt和Bcl-2的表达，抑制FLS凋亡，抑制FLS中活性Caspase 3和Bax的表达。LY-294002处理可部分抑制这种作用。Trx 1可能通过调节PI 3 K-Akt的活化，在RA-FLS的增殖和凋亡中发挥重要作用。
We aimed to investigate the possible effects of thioredoxin 1 (Trx1) on the proliferation and apoptosis of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLSs) and elucidate the possible mechanisms involved. We investigated the distribution and expression of Trx1 in synovial tissues from RA and osteoarthritis (OA) patients by immunohistochemistry and real-time polymerase chain reaction (RT-PCR) analyses. RA-FLSs were isolated and cultured under normoxic (21% oxygen) or hypoxic (3% oxygen) concentrations. Transfection of Trx1-siRNAs and a Trx1 overexpression construct was conducted to manipulate the expression of Trx1. Protein expression was detected by Western blot. Doxorubicin (Adriamycin, ADR) was used to induce apoptosis. LY-294002 was used for the inhibition of PI3K-Akt. Cell proliferation and apoptosis were determined by MTS (3-[4,5-dimethylthiazol-2-yl]-5-[3-carboxymethoxyphenyl]-2-[4-sulfophenyl]-2H-tetrazolium, inner salt) assay and flow cytometry, respectively. The mRNA and protein expression of Trx1 in RA tissues was higher than that in OA tissues. The expression levels of Trx1 and cell proliferation in RA-FLSs were increased under hypoxia in comparison to those under normoxia. In hypoxia, downregulation of Trx1 significantly suppressed FLS proliferation, and the expression of PI3Kp85, phospho-Akt, and Bcl-2, while notably increased FLS apoptosis and the expression of active Caspase3 and Bax. In normoxia, Trx1 overexpression promoted the FLS proliferation and the expression of PI3Kp85, phospho-Akt, and Bcl-2, but inhibited FLS apoptosis and the expression of active Caspase3 and Bax in FLSs. Such effects were partially repressed by LY-294002 treatment. Trx1 may play an important role in regulating the proliferation and apoptosis of RA-FLSs by modulating PI3K-Akt activation.
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影响因子：
1.9
作者：
Sivakumar, Branavan;Akhavani, Mohammed A.;Kang, Norbert
通讯作者：
Kang, Norbert
影响因子：
4.3
作者：
Li, Guo-Qing;Zhang, Yu;Liu, Yan-Qing
通讯作者：
Liu, Yan-Qing
影响因子：
4.9
作者：
Muz B;Khan MN;Kiriakidis S;Paleolog EM
通讯作者：
Paleolog EM
影响因子：
3.6
作者：
Jikimoto, T;Nishikubo, Y;Kumagai, S
通讯作者：
Kumagai, S
影响因子：
3.3
作者：
Sartelet, Herve;Rougemont, Anne-Laure;Vassal, Gilles
通讯作者：
Vassal, Gilles