Endogenous matrix metalloproteinase (MMP)-3 and MMP-9 promote the differentiation and migration of adult neural progenitor cells in response to chemokines.
Endogenous matrix metalloproteinase (MMP)-3 and MMP-9 promote the differentiation and migration of adult neural progenitor cells in response to chemokines.
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DOI：
10.1634/stemcells.2008-0519
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发表时间：
2008-12
期刊：
影响因子：
--
通讯作者：
Zhao X
中科院分区：
文献类型：
--
作者：
Barkho BZ;Munoz AE;Li X;Li L;Cunningham LA;Zhao X
成人神经发生受内在程序和外在刺激的调节。脑室下区成体神经干/祖细胞（aNPC）增殖的增强以及成神经细胞向成体大脑缺血区域的迁移提出了独特的挑战，同时也为了解外在线索诱导的神经源性反应的分子机制提供了机会。基质金属蛋白酶 (MMP) 是已知在细胞外基质重塑和细胞迁移中发挥作用的蛋白酶家族。然而，它们在 aNPC 中的存在及其在损伤引起的 aNPC 迁移中的潜在功能在很大程度上仍未得到探索。在这里，我们证明，为了响应两种损伤诱导的趋化因子，基质细胞衍生因子 1 (SDF-1) 和血管内皮生长因子，aNPC 分化成表达增加水平的 MMP-3 和 MMP-9 的迁移细胞。分化的神经母细胞和星形胶质细胞亚群向趋化因子迁移，而未分化的祖细胞则不迁移。阻断 aNPC 中 MMP-3 或 MMP-9 的表达会干扰 aNPC 的分化和趋化因子诱导的细胞迁移。因此，aNPC 表达的内源性 MMP 对于介导其对外在信号的神经源性反应非常重要。
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.
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