期刊
MOLECULAR AND CELLULAR BIOCHEMISTRY
卷 459, 期 1-2, 页码 141-150出版社
SPRINGER
DOI: 10.1007/s11010-019-03557-0
关键词
Rheumatoid arthritis; Epithelial-mesenchymal transition; Transforming growth factor beta 1; Migration; Invasion
类别
资金
- National Natural Science Foundation of China [81771747, 81801624]
- Natural Science Foundation of Guangdong Province [2017A030313475]
Migration and invasion are important characteristics of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLSs), which are involved in joint damage and contribute to rheumatoid arthritis (RA) pathology. However, the underlying mechanisms remain unclear. Because epithelial-mesenchymal transition (EMT) is a key mechanism related to migration and invasion in cancer cells, we investigated the relationship between EMT and RA-FLSs and explored whether the transforming growth factor beta 1 (TGF-beta 1)/Smad signaling pathway is involved. In vivo, fibroblast-like synoviocytes (FLSs) were isolated from the synovium of RA or osteoarthritis (OA) patients and cultured for 4-8 passages. EMT markers were detected by immunofluorescence and Western blotting. RA-FLSs were treated with TGF-beta 1 or Smad2/3 small interfering RNA (siRNA), EMT markers were detected, and migration and invasion were assessed by Transwell assays. EMT markers could be detected in FLSs; when compared with osteoarthritis fibroblast-like synoviocytes (OA-FLSs), E-cadherin and vimentin decreased, while N-cadherin and alpha-smooth muscle actin (alpha-SMA) increased in RA-FLSs. Furthermore, TGF-beta 1 enhanced migration and invasion by inducing EMT via activating Smad2/3 in RA-FLSs. Phosphorylation of Smad2/3 was accompanied by degradation of Smad3. Silencing Smad2/3 blocked EMT and inhibited the migration and invasion induced by TGF-beta 1. Matrix metalloproteinase 9 (MMP9) and vimentin were not affected when cells were treated with TGF-beta 1 or Smad2/3 siRNA. The TGF-beta 1/Smad signaling pathway is involved in EMT and contributes to migration and invasion in RA-FLSs. Interestingly, vimentin decreased in RA-FLSs, but there is no correlation between vimentin and TGF-beta 1/Smad signaling pathway. Thus, further research on vimentin should be conducted.
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