The role of protein kinase in human synovial fibroblast growth

Biochem Biophys Res Commun. 1995 May 25;210(3):1066-75. doi: 10.1006/bbrc.1995.1765.

Abstract

The histological features of rheumatoid arthritis (RA) consist of overgrowth of synovial cells. Several growth factors that cause synovial hyperplasia have been identified in RA synovium. The basic-fibroblast growth factor (b-FGF), representing one of these growth factors, may play an important role in the pathogenesis of RA. We examined the b-FGF-mediated intracellular signal pathway involved in synovial cell growth. b-FGF-induced synovial cell growth was inhibited by protein tyrosine kinase (PTK) inhibitors, herbimycin A and genistein, but not by H7 that inhibits protein kinase C (PKC). Stimulation of synovial cells with b-FGF resulted in tyrosine phosphorylation of cellular proteins and MAP kinase activation. Our results also demonstrated that b-FGF-mediated activation of MAP kinase was inhibited by herbimycin A indicating that protein tyrosine kinase may be involved in the activation of MAP kinase in human synovial cells. However, inhibition of b-FGF-mediated MAP kinase activation by PKC downregulation did not occur.

Publication types

  • Comparative Study

MeSH terms

  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
  • Arthritis, Rheumatoid / enzymology*
  • Arthritis, Rheumatoid / pathology
  • Benzoquinones
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism
  • Cell Cycle / drug effects
  • Cell Cycle / physiology*
  • Cell Division* / drug effects
  • Cells, Cultured
  • Fibroblast Growth Factor 2 / pharmacology*
  • Fibroblasts / enzymology
  • Genistein
  • Humans
  • Hyperplasia
  • Isoflavones / pharmacology
  • Isoquinolines / pharmacology
  • Kinetics
  • Lactams, Macrocyclic
  • Piperazines / pharmacology
  • Protein Kinase C / antagonists & inhibitors
  • Protein Kinases / metabolism*
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Quinones / pharmacology
  • Rifabutin / analogs & derivatives
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Synovial Membrane / enzymology*
  • Synovial Membrane / pathology*
  • Thymidine / metabolism

Substances

  • Benzoquinones
  • Isoflavones
  • Isoquinolines
  • Lactams, Macrocyclic
  • Piperazines
  • Quinones
  • Fibroblast Growth Factor 2
  • Rifabutin
  • herbimycin
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
  • Genistein
  • Protein Kinases
  • Protein-Tyrosine Kinases
  • Protein Kinase C
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Thymidine