Department of Orthopaedics, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China.
Neuroscience. 2011 Oct 13;193:421-8. doi: 10.1016/j.neuroscience.2011.07.031. Epub 2011 Jul 20.
Matrix metalloproteinase 9 (MMP9) and MMP2 are important in the development and maintenance of neuropathic pain behavior induced by peripheral nerve injury. The enzymatic activity of MMP9 and MMP2 is balanced specifically by tissue inhibitor of metalloproteinase 1 (TIMP1) and TIMP2, respectively. In present study, we measured the effect of peripheral nerve injury on the expression of TIMP1 and TIMP2 in adult dorsal root ganglia (DRG). A dramatic increase of TIMP1 mRNA and a decrease of TIMP2 in DRG after sciatic nerve transection (SNT) were displayed through a real-time PCR method. Furthermore, data showed by in situ hybridization that TIMP1 mRNA was only localized in DRG satellite cells under normal conditions. TIMP1 mRNA was increased in satellite cells, and induced within sensory neurons after SNT. Analysis of neuronal profiles showed that induced TIMP1 mRNA was mainly contained in small and medium DRG neurons. Further study displayed that induced TIMP1 mRNA was predominantly present in activating transcription factor 3 (ATF3)-positive injured DRG neurons. Comparatively, TIMP2 mRNA was mostly contained within sensory neurons and the overall amount decreased at the late stage after nerve injury. These data showed different change of TIMPs in DRG after peripheral nerve injury.
基质金属蛋白酶 9(MMP9)和 MMP2 在周围神经损伤诱导的神经性疼痛行为的发展和维持中很重要。MMP9 和 MMP2 的酶活性分别由基质金属蛋白酶抑制剂 1(TIMP1)和 TIMP2 特异性平衡。在本研究中,我们测量了周围神经损伤对成年背根神经节(DRG)中 TIMP1 和 TIMP2 表达的影响。通过实时 PCR 方法显示,坐骨神经横断(SNT)后 DRG 中的 TIMP1 mRNA 显著增加,TIMP2 减少。此外,原位杂交数据显示,TIMP1 mRNA 仅在正常情况下存在于 DRG 卫星细胞中。SNT 后,TIMP1 mRNA 在卫星细胞中增加,并在感觉神经元中诱导。神经元形态分析显示,诱导的 TIMP1 mRNA 主要存在于中小 DRG 神经元中。进一步的研究显示,诱导的 TIMP1 mRNA 主要存在于激活转录因子 3(ATF3)阳性损伤 DRG 神经元中。相比之下,TIMP2 mRNA 主要存在于感觉神经元中,并且在神经损伤后晚期整体减少。这些数据显示了周围神经损伤后 DRG 中 TIMPs 的不同变化。