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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DOI：
10.1007/s10067-017-3832-1
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Lieying Fan
中科院分区：
文献类型：
--
作者：
Tianbao Lu;Ming Zong;Shasha Fan;Ying Lu;Shanhan Yu;Lieying Fan
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 (RTPCR).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 PI3KAkt..Cell proliferation and apoptosis were determined.by MTS ( 3 - [ 4 , 5 - d i m e t h y l t h i a z o l - 2 - y l ] - 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.
