Veeravalli Krishna Kumar, Dasari Venkata Ramesh, Tsung Andrew J, Dinh Dzung H, Gujrati Meena, Fassett Dan, Rao Jasti S
Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, Peoria, IL 61605, USA.
Neurobiol Dis. 2009 Oct;36(1):200-12. doi: 10.1016/j.nbd.2009.07.012. Epub 2009 Jul 23.
Matrix metalloproteinases (MMPs) are a large family of proteolytic enzymes involved in inflammation, wound healing and other pathological processes after neurological disorders. MMP-2 promotes functional recovery after spinal cord injury (SCI) by regulating the formation of a glial scar. In the present study, we aimed to investigate the expression and/or activity of several MMPs, after SCI and human umbilical cord blood mesenchymal stem cell (hUCB) treatment in rats with a special emphasis on MMP-2. Treatment with hUCB after SCI altered the expression of several MMPs in rats. MMP-2 is upregulated after hUCB treatment in spinal cord injured rats and in spinal neurons injured either with staurosporine or hydrogen peroxide. Further, hUCB induced upregulation of MMP-2 reduced formation of the glial scar at the site of injury along with reduced immunoreactivity to chondroitin sulfate proteoglycans. Blockade of MMP-2 activity in hUCB cocultured injured spinal neurons reduced the protection offered by hUCB which indicated the involvement of MMP-2 in the neuroprotection offered by hUCB. Based on these results, we conclude that hUCB treatment after SCI upregulates MMP-2 levels and reduces the formation of the glial scar thereby creating an environment suitable for endogenous repair mechanisms.
基质金属蛋白酶（MMPs）是一类庞大的蛋白水解酶家族，参与炎症、伤口愈合及神经功能紊乱后的其他病理过程。MMP-2通过调节胶质瘢痕的形成促进脊髓损伤（SCI）后的功能恢复。在本研究中，我们旨在调查大鼠SCI及人脐带血间充质干细胞（hUCB）治疗后几种MMPs的表达和/或活性，特别关注MMP-2。SCI后用hUCB治疗改变了大鼠几种MMPs的表达。脊髓损伤大鼠以及用星形孢菌素或过氧化氢损伤的脊髓神经元经hUCB治疗后，MMP-2表达上调。此外，hUCB诱导的MMP-2上调减少了损伤部位胶质瘢痕的形成，同时降低了对硫酸软骨素蛋白聚糖的免疫反应性。在与hUCB共培养的损伤脊髓神经元中阻断MMP-2活性会降低hUCB提供的保护作用，这表明MMP-2参与了hUCB提供的神经保护作用。基于这些结果，我们得出结论，SCI后用hUCB治疗可上调MMP-2水平并减少胶质瘢痕的形成，从而创造一个适合内源性修复机制的环境。
