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Transforming growth factor [beta]1 promotes fibroblast-like synoviocytes migration and invasion via TGF-[beta]1/Smad signaling in rheumatoid arthritis
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...
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Published in: | Molecular and cellular biochemistry 2019-09, Vol.459 (1-2), p.141 |
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Main Authors: | , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Online Access: | Get full text |
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Summary: | 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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ISSN: | 0300-8177 |
DOI: | 10.1007/s11010-019-03557-0 |