Zhou Ying, Cui Zhiming, Xia Xiaopeng, Liu Chun, Zhu Xinhui, Cao Jianhua, Wu Yuanyuan, Zhou Li, Ben Zhiyun, Song Yan, Zhang Haiyan, Zhang Dongmei
Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Department of Immunology, Medical College, Nantong University, Nantong, 226001, People's Republic of China.
Cell Mol Neurobiol. 2014 Nov;34(8):1151-63. doi: 10.1007/s10571-014-0090-5. Epub 2014 Jul 30.
Matrix metalloproteinase-1 (MMP-1), a member of the matrix metalloproteinases family, plays an integral role in extracellular matrix degradation and has been reportedly involved in the regulation of the brain or spinal cord traumatic neurovascular remodeling. Although the critical involvement of MMP-1 in the metastasis of tumors has been extensively documented, the role of MMP-1 in the pathology of neurological diseases remains largely elusive. In the present study, we established an adult rat spinal cord injury (SCI) model and investigated a potential role of MMP-1 in the pathological process of SCI. Using Western blot analysis, we identified notable expression change of MMP-1 after SCI. Immunohistochemistry showed that MMP-1 was distributed widely in rat spinal cord. Double immunofluorescence staining revealed that MMP-1 immunoreactivity was predominantly increased in neurons and astrocytes following SCI. Moreover, after injury, colocalization of MMP-1/active caspase-3 in neurons (NeuN-positive), and colocalization of MMP-1/PCNA in astrocytes (GFAP-positive) were clearly observed. We also examined the protein expression of PCNA, active caspase-3, Bcl-2, and Bax and found that the expression of the proteins was closely correlated with that of MMP-1. Taken together, our findings indicate that MMP-1 might play an important role in the regulation of neuronal apoptosis and astrocyte proliferation after SCI.
基质金属蛋白酶-1(MMP-1)是基质金属蛋白酶家族的一员,在细胞外基质降解中发挥着不可或缺的作用,据报道还参与脑或脊髓创伤性神经血管重塑的调节。尽管MMP-1在肿瘤转移中的关键作用已得到广泛记录,但MMP-1在神经疾病病理学中的作用仍 largely 难以捉摸。在本研究中,我们建立了成年大鼠脊髓损伤(SCI)模型,并研究了MMP-1在SCI病理过程中的潜在作用。通过蛋白质印迹分析,我们确定了SCI后MMP-1的显著表达变化。免疫组织化学显示MMP-1广泛分布于大鼠脊髓中。双重免疫荧光染色显示,SCI后神经元和星形胶质细胞中MMP-1免疫反应性主要增加。此外,损伤后,在神经元(NeuN阳性)中明显观察到MMP-1/活性半胱天冬酶-3的共定位,在星形胶质细胞(GFAP阳性)中明显观察到MMP-1/增殖细胞核抗原(PCNA)的共定位。我们还检测了PCNA、活性半胱天冬酶-3、Bcl-2和Bax的蛋白表达,发现这些蛋白的表达与MMP-1的表达密切相关。综上所述,我们的研究结果表明,MMP-1可能在SCI后神经元凋亡和星形胶质细胞增殖的调节中发挥重要作用。