Monocyte chemoattractant protein‑1 promotes the proliferation, migration and differentiation potential of fibroblast‑like synoviocytes via the PI3K/P38 cellular signaling pathway

  • Authors:
    • Xiang Tong
    • Huangjian Zeng
    • Pengchen Gu
    • Kai Wang
    • Han Zhang
    • Xiangjin Lin
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  • Published online on: January 29, 2020     https://doi.org/10.3892/mmr.2020.10969
  • Pages: 1623-1632
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Abstract

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation of the joints and joint destruction. Monocyte chemoattractant protein 1 (MCP‑1) is highly expressed in the joints of patients suffering from RA. The present study aimed to evaluate the effects of MCP‑1 on the phenotype of fibroblast‑like synoviocytes (FLSs) and their differentiation potential towards vascular endothelial cells. The expression of MCP‑1 in collagen‑induced arthritis (CIA) rats was investigated by PCR, ELISA and immunohistology. Cell proliferation induced by MCP‑1 was measured using a Cell Counting Kit‑8 (CCK‑8) and 5‑Bromo‑2‑deoxyuridine ELISA assay. In addition, the effects of MCP‑1 on the migration of FLSs was examined using a Transwell assay. Activation of PI3K and P38 were investigated by western blotting following MCP‑1 treatment. The vascular endothelial cell markers, tumor necrosis factor α (TNF‑α) and interleukin‑1 β (IL‑β), were also examined by western blotting. LY294002 [PI3K inhibitor, (LY)] and SB203580 [P38 inhibitor, (SB)] were used to examine the proliferative and pro‑differentiation effect of PI3K and P38. The present findings showed that the expression level of MCP‑1 in the synovium of CIA rats was significantly higher compared with controls. The present in vitro study suggested that MCP‑1 increased the FLSs cell numbers with a maximal effect at 200 ng/ml, and induced the maximal phosphorylation of PI3K at 15 min and P38 at 30 min. In addition, MCP‑1 stimulation significantly increased the migration of FLSs. Furthermore, MCP‑1‑induced the expression of vascular endothelial growth factor and CD31 in FLSs. Suppression of PI3K and P38 was found to reduce MCP‑1 induced FLSs proliferation and migration, and decreased the expression levels of angiogenesis markers increased following MCP‑1 treatment. MCP‑1 was also found to increase the expression levels of both TNF‑α and IL‑β. Therefore, MCP‑1 could promote the proliferation and migration of FLSs, and was found to increase the expression levels of various angiogenesis markers via PI3K/P38, suggesting a role for this pathway in synovium hyperplasia in RA.
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March 2020
Volume 21 Issue 3

Print ISSN: 1791-2997
Online ISSN:1791-3004

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APA
Tong, X., Zeng, H., Gu, P., Wang, K., Zhang, H., & Lin, X. (2020). Monocyte chemoattractant protein‑1 promotes the proliferation, migration and differentiation potential of fibroblast‑like synoviocytes via the PI3K/P38 cellular signaling pathway. Molecular Medicine Reports, 21, 1623-1632. https://doi.org/10.3892/mmr.2020.10969
MLA
Tong, X., Zeng, H., Gu, P., Wang, K., Zhang, H., Lin, X."Monocyte chemoattractant protein‑1 promotes the proliferation, migration and differentiation potential of fibroblast‑like synoviocytes via the PI3K/P38 cellular signaling pathway". Molecular Medicine Reports 21.3 (2020): 1623-1632.
Chicago
Tong, X., Zeng, H., Gu, P., Wang, K., Zhang, H., Lin, X."Monocyte chemoattractant protein‑1 promotes the proliferation, migration and differentiation potential of fibroblast‑like synoviocytes via the PI3K/P38 cellular signaling pathway". Molecular Medicine Reports 21, no. 3 (2020): 1623-1632. https://doi.org/10.3892/mmr.2020.10969