Endogenous matrix metalloproteinase (MMP)-3 and MMP-9 promote the differentiation and migration of adult neural progenitor cells in response to chemokines.
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.
Barkho
Basam Z
BZ
Department of Neurosciences, University of New Mexico School of Medicine, Albuquerque, New Mexico 87131, USA.
Munoz
Ari E
AE
Li
Xuekun
X
Li
Lu
L
Cunningham
Lee Anna
LA
Zhao
Xinyu
X
D000818:Animals; D002454:Cell Differentiation; D002465:Cell Movement; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism*; D006801:Humans; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology; D016086:Lentivirus / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D051379:Mice; D009474:Neurons / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D018925:Chemokines; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; D019278:Matrix Metalloproteinase 3; D020780:Matrix Metalloproteinase 9