TWEAK-Fn14 Influences Neurogenesis Status via Modulating NF-κB in Mice with Spinal Cord Injury.

The aim of our research is to investigate the regulatory role of TNF-like weak inducer of apoptosis- fibroblast growth factor–inducible 14 (TWEAK-Fn14) pathway in nuclear factor-kappa B (NF-κB) expression and neurogenesis status after spinal cord injury (SCI). We constructed a mice model of spinal cord injury and injected different lentiviral vectors which were transfected with TWEAK, TWEAK small interfering RNA (siRNA) and Fn14 siRNA into different groups of mice. Locomotor functional recovery status of the hind limb in mice was assessed using the Basso, Beattie and Bresnahan (BBB) test. Apoptosis status in the injured area was examined via TDT-mediated dUTP-biotin nick end-labeling (TUNEL) staining, the expression of GAP-43 in injured spinal cord was quantified by immunohistochemistry and expressions of TWEAK, Fn14, NF-κB, TNF-α, and IL-1β were evaluated by either western blot or ELISA. The expressions of TWEAK, Fn14, and NF-κB in the model group were significantly higher compared with those in the control group. Furthermore, the TWEAK group in which TWEAK was overexpressed exhibited significantly higher expressions of TWEAK, Fn14, and NF-κB, TNF-α and IL-1β in relation to those in the model group (P < 0.05 for all). Moreover, the transfection of Fn14 siRNA antagonized the above effect of TWEAK transfection on injured mice. On the other hand, the TWEAK siRNA group in which the expression of TWEAK was inhibited exhibited significantly lower expressions of TWEAK, Fn14, NF-κB, TNF-α, and IL-1β (P < 0.05 for all). Moreover, the transfection of TWEAK siRNA enhanced the locomotor functional recovery status in injured mice and suppressed the apoptosis of injured areas (P < 0.05 for all). In conclusion, stimulating the TWEAK-Fn14 pathway may elevate the expression of NF-κB, thereby slow the function recovery of SCI mice whereas inhibiting the TWEAK-Fn14 pathway may improve the neurogenesis status in mice with spinal cord injuries.