Transforming growth factor β1 promotes fibroblast-like synoviocytes migration and invasion via TGF-β1/Smad signaling in rheumatoid arthritis

波形蛋白 SMAD公司 上皮-间质转换 转化生长因子 癌症研究 化学 信号转导 成纤维细胞 小干扰RNA 基因沉默 MMP9公司 细胞迁移 生物 细胞生物学 免疫学 医学 内科学 转染 转移 下调和上调 癌症 细胞 免疫组织化学 体外 基因 生物化学
作者
Dingji Zhu,Jian Zhao,Aiju Lou,Qin Huang,Qian Ouyang,Ji-Xiao Zhu,Moli Fan,YingQiong He,Hao Ren,Min Yang
出处
期刊:Molecular and Cellular Biochemistry [Springer Nature]
卷期号:459 (1-2): 141-150 被引量:28
标识
DOI:10.1007/s11010-019-03557-0
摘要

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 β1 (TGF-β1)/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-β1 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 α-smooth muscle actin (α-SMA) increased in RA-FLSs. Furthermore, TGF-β1 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-β1. Matrix metalloproteinase 9 (MMP9) and vimentin were not affected when cells were treated with TGF-β1 or Smad2/3 siRNA. The TGF-β1/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-β1/Smad signaling pathway. Thus, further research on vimentin should be conducted.
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