期刊
STEM CELLS
卷 26, 期 12, 页码 3139-3149出版社
WILEY
DOI: 10.1634/stemcells.2008-0519
关键词
Neural stem cells; Adult neurogenesis; Chemokines; Migration; Matrix metalloproteinase; Differentiation
资金
- NIH [MH080434, MH078972, P20RR15636]
- American Heart Association Predoctoral Fellowship [0810123Z]
- Autism Speaks Postdoctoral Fellowship
- NIH/Institutional Minority Student Development program [IMSD GM060201]
- NATIONAL CENTER FOR RESEARCH RESOURCES [P20RR015636] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R25GM060201] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF MENTAL HEALTH [R01MH078972, R01MH080434] Funding Source: NIH RePORTER
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. STEM CELLS 2008;26:3139-3149
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