Disruption of Nrf2 enhances the upregulation of nuclear factor-kappaB activity, tumor necrosis factor-α, and matrix metalloproteinase-9 after spinal cord injury in mice.
Matrix metalloproteinase-9 (MMP-9) plays an important role in the acute periods of spinal cord injury (SCI), and its expression is related to the inflammation which could cause the disruption of the blood-spinal barrier (BBB). Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key transcription factor that plays a crucial role in cytoprotection against inflammation. The present study investigated the role of Nrf2 in upregulating of nuclear factor kappa B (NF-κB) activity, tumor necrosis factor-α (TNF-α), and MMP-9 after SCI. Wild-type Nrf2 (+/+) and Nrf2-deficient (Nrf (-/-)) mice were subjected to an SCI model induced by the application of vascular clips (force of 10 g) to the dura after a three-level T8-T10 laminectomy. We detected the wet/dry weight ratio of impaired spinal cord tissue, the activation of NF-κB, the mRNA and protein levels of TNF-α and MMP-9, and the enzyme activity of MMP-9. Nrf2 (-/-) mice were demonstrated to have more spinal cord edema, NF-κB activation, TNF-α production, and MMP-9 expression after SCI compared with the wild-type controls. The results suggest that Nrf2 may play an important role in limiting the upregulation of NF-κB activity, TNF-α, and MMP-9 in spinal cord after SCI.
Mao
Lei
L
Department of Neurosurgery, School of Medicine, Jinling Hospital, Nanjing University, Nanjing, Jiangsu 210002, China.
Wang
Handong
H
Qiao
Liang
L
Wang
Xiaoliang
X
D000818:Animals; D005838:Genotype; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D013119:Spinal Cord Injuries / Q000378:metabolism* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; C495636:Nfe2l2 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D020780:Matrix Metalloproteinase 9