Gastrin-releasing peptide and its receptor increase arthritis fibroblast-like synoviocytes invasiveness through activating the PI3K/AKT pathway

Vanessa Schuck Clarimundo, Mirian Farinon, Renata Ternus Pedó, Vivian Oliveira Nunes Teixeira, Carolina Nör, Percio S. Gulko, Ricardo Machado Xavier, Patricia Gnieslaw de Oliveira

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Rheumatoid arthritis (RA) is an autoimmune disease that leads to joint destruction. The fibroblast-like synoviocytes (FLS) has a central role on the disease pathophysiology. The present study aimed to examine the role of gastrin-releasing peptide (GRP) and its receptor (GRPR) on invasive behavior of mice fibroblast-like synoviocytes (FLS), as well as to evaluate GRP-induced signaling on PI3K/AKT pathway. The expression of GRPR in FLS was investigated by immunocytochemistry, western blot (WB) and qRT-PCR. The proliferation and invasion were assessed by SRB and matrigel-transwell assay after treatment with GRP and/or RC-3095 (GRPR antagonist), and/or Ly294002 (inhibitor of PI3K/AKT pathway). Finally, AKT phosphorylation was assessed by WB. GRPR protein was detected in FLS and the exposure to GRP increased FLS invasion by nearly two-fold, compared with untreated cells (p < 0.05), while RC-3095 reversed that effect (p < 0.001). GRP also increased phosphorylated AKT expression in FLS. When Ly294002 was added with GRP, it prevented the GRP-induced increased cell invasiveness (p < 0.001). These data suggest that GRPR expression in FLS and that exogenous GRP are able to activate FLS invasion. This effect occurs at least in part through the AKT activation. Therefore, understanding of the GRP/GRPR pathway could be relevant in the development of FLS-targeted therapy for RA.

Original languageEnglish
Pages (from-to)57-61
Number of pages5
JournalPeptides
Volume95
DOIs
StatePublished - Sep 2017

Keywords

  • Fibroblasts-like synoviocyte
  • Gastrin-releasing peptide receptor
  • PI3K/AKT pathway
  • RC-3095
  • Rheumatoid arthritis

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