UPAR promotes tumor-like biologic behaviors of fibroblast-like synoviocytes through PI3K/Akt signaling pathway in patients with rheumatoid arthritis

Yan Liu, Yun Feng Pan, You Qiu Xue, Lin Kai Fang, Xing Hua Guo, Xin Guo, Meng Liu, Bi Yao Mo, Meng Ru Yang, Fang Liu, Yun Ting Wu, Nancy Olsen, Song Guo Zheng

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Urokinase-type plasminogen activator receptor (uPAR), is a multifunctional receptor on cell surface, widely present in endothelial cells, fibroblasts, and a variety of malignant cells. Current studies have suggested that uPAR overexpressed on synovial tissues or in synovial fluid or plasma in patients with rheumatoid arthritis (RA). However, there are limited researches regarding the role of uPAR on fibroblast-like synoviocytes of rheumatoid arthritis (RA-FLSs) and its underlying mechanisms. Here, our studies show that the expression of uPAR protein was significantly higher in fibroblast-like synoviocytes (FLSs) from RA than those from osteoarthritis or traumatic injury patients. uPAR gene silencing significantly inhibited RA-FLSs cell proliferation, restrained cell transformation from the G0/G1 phase to S phase, aggravated cell apoptosis, interfered with RA-FLSs cell migration and invasion, and reduced activation of the PI3K/Akt signaling pathway, which may be associated with β1-integrin. Cell supernatants from uPAR gene-silenced RA-FLSs markedly inhibited the migration and tubule formation ability of the HUVECs (a human endothelial cell line). Therefore, we demonstrate that uPAR changes the biological characteristics of RA-FLSs, and affects neoangiogenesis of synovial tissues in patients with RA. All of these may be associated with the β1-integrin/PI3K/Akt signaling pathway. These results imply that targeting uPAR and its downstream signal pathway may provide therapeutic effects in RA.

Original languageEnglish (US)
Pages (from-to)171-181
Number of pages11
JournalCellular and Molecular Immunology
Volume15
Issue number2
DOIs
StatePublished - Feb 1 2018

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Fingerprint Dive into the research topics of 'UPAR promotes tumor-like biologic behaviors of fibroblast-like synoviocytes through PI3K/Akt signaling pathway in patients with rheumatoid arthritis'. Together they form a unique fingerprint.

  • Cite this

    Liu, Y., Pan, Y. F., Xue, Y. Q., Fang, L. K., Guo, X. H., Guo, X., Liu, M., Mo, B. Y., Yang, M. R., Liu, F., Wu, Y. T., Olsen, N., & Zheng, S. G. (2018). UPAR promotes tumor-like biologic behaviors of fibroblast-like synoviocytes through PI3K/Akt signaling pathway in patients with rheumatoid arthritis. Cellular and Molecular Immunology, 15(2), 171-181. https://doi.org/10.1038/cmi.2016.60