Lentivirus-mediated silencing of the CTGF gene suppresses the formation of glial scar tissue in a rat model of spinal cord injury

Abstract

Background ContextOne of the many reactive changes following a spinal cord injury (SCI) is the formation of a glial scar, a reactive cellular process whereby glial cells accumulate and surround the central nervous system injury sites to seal in the wound. Thus, the inhibition of glial scar is of great importance for SCI recovery. PurposeThis study aimed to explore the effect of lentivirus-mediated silencing of the CTGF gene on the formation of glial scar tissue in a rat model of SCI. Study DesignThis is a prospective study. Study SampleA total of 56 Wistar female rats aged 8 weeks were randomly selected for this study. Outcome MeasuresThe motor function of the rats was assessed using the Basso, Beattie, and Bresnahan (BBB) functional scale, footprint analysis of gait, and the Basso Mouse Scale (BMS). Quantitative real-time polymerase chain reaction, Western blotting, and immunohistochemistry were performed to detect the mRNA and protein expressions of glial fibrillary acidic protein (GFAP), vimentin, fibronectin, and laminin in the spinal cord tissues. MethodsA rat model of SCI was successfully established. Fifty-six male Wistar rats were randomly selected and assigned into four groups (14 rats in each group): the sham operation group, the SCI model group, the negative control (NC) group (SCI rats transfected with empty vector plasmids), and the siRNA-CTGF group (SCI rats transfected with lentivirus CTGF siRNA). ResultsThe SCI rats showed decreased activity and were dragging their bodies while moving. Compared with the sham operation group, the BBB and BMS scores in the SCI model, NC, and siRNA-CTGF groups significantly decreased. However, the BBB and BMS scores in the siRNA-CTGF group were higher than those in the SCI model and NC groups. The mRNA and protein expressions of GFAP, vimentin, fibronectin, and laminin significantly increased in the SCI model, NC, and siRNA-CTGF groups in comparison with those in the sham operation group. Furthermore, the mRNA and protein expressions of GFAP, vimentin, fibronectin, and laminin in the siRNA-CTGF group were lower than those in the SCI model and NC groups 28 days after transfection. ConclusionsThese findings indicate that lentivirus-mediated silencing of the CTGF gene can suppress the formation of glial scar tissue after SCI.