Endogenous matrix metalloproteinase (MMP)-3 and MMP-9 promote the differentiation and migration of adult neural progenitor cells in response to chemokines

Stem Cells. 2008 Dec;26(12):3139-49. doi: 10.1634/stemcells.2008-0519. Epub 2008 Sep 25.


Adult neurogenesis is regulated by both intrinsic programs and extrinsic stimuli. The enhanced proliferation of adult neural stem/progenitor cells (aNPCs) in the subventricular zone and the migration of neuroblasts toward the ischemic region in adult brains present a unique challenge as well as an opportunity to understand the molecular mechanisms underlying the extrinsic cue-induced neurogenic responses. Matrix metalloproteinases (MMPs) are a family of proteinases known to play a role in extracellular matrix remodeling and cell migration. However, their presence in aNPCs and their potential function in injury-induced aNPC migration remain largely unexplored. Here we demonstrate that in response to two injury-induced chemokines, stromal cell-derived factor 1 (SDF-1) and vascular endothelial growth factor, aNPCs differentiated into migratory cells that expressed increased levels of MMP-3 and MMP-9. Whereas differentiated neuroblasts and a subpopulation of astrocytes migrated toward the chemokines, undifferentiated progenitors did not migrate. Blocking the expression of MMP-3 or MMP-9 in aNPCs interfered with both the differentiation of aNPCs and chemokine-induced cell migration. Thus, endogenous MMPs expressed by aNPCs are important for mediating their neurogenic response to extrinsic signals.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Movement
  • Cells, Cultured
  • Chemokines / metabolism*
  • Humans
  • Infarction, Middle Cerebral Artery / pathology
  • Lentivirus / metabolism
  • Matrix Metalloproteinase 3 / metabolism*
  • Matrix Metalloproteinase 9 / metabolism*
  • Mice
  • Neurons / metabolism*
  • Recombinant Proteins / metabolism
  • Stem Cells / cytology
  • Stem Cells / metabolism*
  • Vascular Endothelial Growth Factor A / metabolism


  • Chemokines
  • Recombinant Proteins
  • Vascular Endothelial Growth Factor A
  • Matrix Metalloproteinase 3
  • Matrix Metalloproteinase 9