Matrix metalloproteinase-9 is up-regulated by CCL19/CCR7 interaction via PI3K/Akt pathway and is involved in CCL19-driven BMSCs migration

Biochem Biophys Res Commun. 2014 Aug 22;451(2):222-8. doi: 10.1016/j.bbrc.2014.07.112. Epub 2014 Jul 30.

Abstract

C-C chemokine receptor 7 (CCR7) and its ligands CCL19 contributes to the directional migration of certain cancer cell lines, but its role in the migration of BMSCs remains vague. The aim of this study was to determine the possible interaction between CCL19-induced conditions and matrix metalloproteinases-9 (MMP9) expression in BMSCs. Cell migration using Transwell assay indicated that activation of CCR7 by its specific ligand, exogenous chemokine ligand 19 (CCL19), was associated with a significant linear increase. Western blot and real-time PCR indicated that CCL19/CCR7 significantly upregulated expression of MMP9, which is related to metastasis-associated genes. The CCL19/CCR7 interaction significantly enhanced phosphorylation of Akt, as measured by Western blot. P-Akt and MMP9 protein expression exhibited a time-dependent pattern, and the peak was at 48h. LY294002 significantly abolished the effects of exogenous CCL19. These results suggest that CCL19/CCR7 contributes to the migration of BMSCs by upregulating MMP9 potentially via the PI3K/Akt pathway.

Keywords: BMSCs; CCL19; CCR7; MMP9; Migration; P-Akt.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Movement / drug effects
  • Cell Movement / immunology
  • Cell Movement / physiology
  • Cells, Cultured
  • Chemokine CCL19 / metabolism*
  • Chromones / pharmacology
  • Gene Knockdown Techniques
  • Matrix Metalloproteinase 9 / metabolism*
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / physiology*
  • Morpholines / pharmacology
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphoinositide-3 Kinase Inhibitors
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA, Small Interfering / genetics
  • Rats
  • Receptors, CCR7 / antagonists & inhibitors
  • Receptors, CCR7 / genetics
  • Receptors, CCR7 / metabolism*
  • Signal Transduction
  • Up-Regulation

Substances

  • Ccr7 protein, rat
  • Chemokine CCL19
  • Chromones
  • Morpholines
  • Phosphoinositide-3 Kinase Inhibitors
  • RNA, Small Interfering
  • Receptors, CCR7
  • 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
  • Proto-Oncogene Proteins c-akt
  • Matrix Metalloproteinase 9
  • Mmp9 protein, rat