Abstract:
: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.
journal_name
Clin Rheumatoljournal_title
Clinical rheumatologyauthors
Lu T,Zong M,Fan S,Lu Y,Yu S,Fan Ldoi
10.1007/s10067-017-3832-1subject
Has Abstractpub_date
2018-01-01 00:00:00pages
117-125issue
1eissn
0770-3198issn
1434-9949pii
10.1007/s10067-017-3832-1journal_volume
37pub_type
杂志文章abstract::A 78-year-old Japanese woman with Sjögren's syndrome complicating immune-mediated aplastic anaemia is described. A diagnosis of aplastic anaemia was made from severe pancytopenia with hypoplastic marrow. Laboratory studies suggested an association of bone marrow suppressive T-lymphocytes with the pathogenesis of aplas...
journal_title:Clinical rheumatology
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pub_type: 临床试验,杂志文章,随机对照试验
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