Role of c-Jun N-terminal kinase in the PDGF-induced proliferation and migration of human adipose tissue-derived mesenchymal stem cells

J Cell Biochem. 2005 Aug 15;95(6):1135-45. doi: 10.1002/jcb.20499.

Abstract

Platelet-derived growth factor (PDGF) is a critical regulator of proliferation and migration for mesenchymal type cells. In this study, we examined the role of mitogen-activated protein (MAP) kinases in the PDGF-BB-induced proliferation and migration of human adipose tissue-derived mesenchymal stem cells (hATSCs). The PDGF-induced proliferation was prevented by a pretreatment with the c-Jun N-terminal kinase (JNK) inhibitor, SP600125. However, it was not prevented by a pretreatment with a p38 MAP kinase inhibitor, SB202190, and a specific inhibitor of the upstream kinase of extracellular signal-regulated kinase (ERK1/2), U0126. Treatment with PDGF induced the activation of JNK and ERK in hATSCs, and pretreatment with SP600125 specifically inhibited the PDGF-induced activation of JNK. Treatment with PDGF induced the cell cycle transition from the G0/G1 phase to the S phase, the elevated expression of cyclin D1, and the phosphorylation of Rb, which were prevented by a pretreatment with SP600125. In addition, the PDGF-induced migration of hATSCs was completely blocked by a pretreatment with SP600125, but not with U0126 and SB202190. These results suggest that JNK protein kinase plays a key role in the PDGF-induced proliferation and migration of mesenchymal stem cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / cytology*
  • Adipose Tissue / drug effects*
  • Adipose Tissue / enzymology
  • Becaplermin
  • Cell Cycle / drug effects
  • Cell Differentiation / drug effects
  • Cell Lineage / drug effects
  • Cell Movement / drug effects*
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Cyclin D1 / metabolism
  • Humans
  • JNK Mitogen-Activated Protein Kinases / metabolism*
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / drug effects*
  • Mesenchymal Stem Cells / enzymology*
  • Osteogenesis / drug effects
  • Phosphorylation / drug effects
  • Platelet-Derived Growth Factor / pharmacology*
  • Proto-Oncogene Proteins c-sis
  • Time Factors

Substances

  • Platelet-Derived Growth Factor
  • Proto-Oncogene Proteins c-sis
  • Cyclin D1
  • Becaplermin
  • JNK Mitogen-Activated Protein Kinases