Pastrana Erika, Moreno-Flores Maria Teresa, Gurzov Esteban N, Avila Jesus, Wandosell Francisco, Diaz-Nido Javier
Centro de Biologia Molecular Severo Ochoa, Universidad Autonoma de Madrid, 28049 Madrid, Spain.
J Neurosci. 2006 May 17;26(20):5347-59. doi: 10.1523/JNEUROSCI.1111-06.2006.
The molecular mechanisms used by olfactory ensheathing cells (OECs) to promote repair in the damaged adult mammalian CNS remain unknown. Thus, we used microarrays to analyze three OEC populations with different capacities to promote axonal regeneration in cultured rat retinal neurons. Gene expression in "long-term cultured OECs" that do not stimulate adult axonal outgrowth was compared with that of "primary olfactory ensheathing cells" and the immortalized OEC cell line TEG3. In this way, we identified a number of candidate genes that might play a role in promoting adult axonal regeneration. Among these genes, it was striking that both the matrix metalloproteinase 2 (MMP2) and an inhibitor of this protease were represented. The disruption of MMP2 activity in TEG3 cells impaired their capacity to trigger axon regeneration in cultured adult retinal neurons. Furthermore, the MMP2 protein was detected in grafts of OECs that elicited robust axonal regeneration in the injured spinal cord of adult rats in vivo. These data suggest that MMP2 does indeed participate in adult axonal regeneration induced by OECs.
嗅鞘细胞（OECs）用于促进成年哺乳动物受损中枢神经系统修复的分子机制尚不清楚。因此，我们使用微阵列分析了三种在培养的大鼠视网膜神经元中具有不同促进轴突再生能力的OEC群体。将不刺激成年轴突生长的“长期培养的OECs”的基因表达与“原代嗅鞘细胞”和永生化OEC细胞系TEG3的基因表达进行了比较。通过这种方式，我们鉴定出了一些可能在促进成年轴突再生中发挥作用的候选基因。在这些基因中，基质金属蛋白酶2（MMP2）及其一种蛋白酶抑制剂均有表达，这一点令人瞩目。TEG3细胞中MMP2活性的破坏损害了它们在培养的成年视网膜神经元中触发轴突再生的能力。此外，在成年大鼠体内损伤脊髓中引发强大轴突再生的OEC移植体中检测到了MMP2蛋白。这些数据表明MMP2确实参与了由OECs诱导的成年轴突再生。
