title: Endogenous matrix metalloproteinase (MMP)-3 and MMP-9 promote the differentiation and migration of adult neural progenitor cells in response to chemokines.
abstract: 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.
authors.affiliation: Department of Neurosciences, University of New Mexico School of Medicine, Albuquerque, New Mexico 87131, USA.
authors.forename: Basam Z
authors.initials: BZ
authors.lastname: Barkho
authors.forename: Ari E
authors.initials: AE
authors.lastname: Munoz
authors.forename: Xuekun
authors.initials: X
authors.lastname: Li
authors.forename: Lu
authors.initials: L
authors.lastname: Li
authors.forename: Lee Anna
authors.initials: LA
authors.lastname: Cunningham
authors.forename: Xinyu
authors.initials: X
authors.lastname: Zhao
mesh_terms: 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
chemical_list: D018925:Chemokines; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; D019278:Matrix Metalloproteinase 3; D020780:Matrix Metalloproteinase 9