Transforming growth factor [beta]1 promotes fibroblast-like synoviocytes migration and invasion via TGF-[beta]1/Smad signaling in rheumatoid arthritis

• Published in: Molecular and cellular biochemistry 2019-09, Vol.459 (1-2), p.141
• Main Authors: Zhu, DingJi, Zhao, JinJun, Lou, AiJu, Huang, Qin, OuYang, QingQing, Zhu, JunQing, Fan, MeiDa
• Format: Article
• Language: English
• Subjects: Bone morphogenetic proteins; Osteoarthritis; Rheumatoid factor; Stem cells; Transforming growth factors
• ISSN: 0300-8177
• DOI: 10.1007/s11010-019-03557-0

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.