MiR-338-5p Promotes Inflammatory Response of Fibroblast-Like Synoviocytes in Rheumatoid Arthritis via Targeting SPRY1

J Cell Biochem. 2017 Aug;118(8):2295-2301. doi: 10.1002/jcb.25883. Epub 2017 Mar 3.

Abstract

Our purpose is to study the roles of microRNA-338-5p (miR-338-5p) on the proliferation, invasion, and inflammatory response of fibroblast-like synoviocytes (SFs) in rheumatoid arthritis patients by regulating SPRY1. The target relationship between miR-338-5p and SPRY1 was validated through luciferase reporter system. The expression of miR-338-5p and SPRY1 in synovial tissues and synovial cells were detected using RT-PCR and western blot. The mimics and inhibitors of miR-338-5p were transfected into SFs. MTT, Transwell, and ELISA assays were used to analyze cell proliferation, invasiveness, and the secreted extracellular pro-inflammatory cytokines (such as IL-1a, IL-6, COX2) levels of SFs. MiR-338-5p was highly expressed in rheumatoid arthritis tissues and cells, and directly down-regulated the expression of SPRY1 in the SFs of rheumatoid arthritis patients. Cell proliferation, invasiveness and the expression level of pro-inflammatory cytokines in synovial cells increased after the transfection of miR-338-5p mimics, while the proliferation, invasion and expression level of pro-inflammatory cytokines decreased after the transfection of miR-338-5p inhibitors. In conclusion,miR-338-5p promoted the proliferation, invasion and inflammatory reaction in SFs of rheumatoid arthritis by directly down-regulating SPRY1 expression. J. Cell. Biochem. 118: 2295-2301, 2017. © 2017 Wiley Periodicals, Inc.

Keywords: FIBROBLAST-LIKE SYNOVIAL CELLS (SFs); MIR-338-5p; RHEUMATOID ARTHRITIS; SPRY1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arthritis, Rheumatoid / chemically induced
  • Arthritis, Rheumatoid / immunology*
  • Arthritis, Rheumatoid / metabolism*
  • Blotting, Western
  • Cell Proliferation / genetics
  • Cell Proliferation / physiology
  • Cells, Cultured
  • Collagen / toxicity
  • Cyclooxygenase 2 / metabolism
  • Fibroblasts / cytology
  • Fibroblasts / metabolism
  • Humans
  • Interleukin-1alpha / metabolism
  • Interleukin-6 / metabolism
  • Male
  • Mice
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Synovial Membrane / cytology
  • Synovial Membrane / metabolism
  • Synoviocytes / cytology*
  • Synoviocytes / metabolism*

Substances

  • Interleukin-1alpha
  • Interleukin-6
  • MIRN338 microRNA, human
  • MicroRNAs
  • Collagen
  • Cyclooxygenase 2
  • PTGS2 protein, human