Investigating How Thbs4 Regulates Degeneration and Regeneration of the Peripheral Nerve

Objective: Molecular biology techniques were employed to investigate the effects of thrombospondin-4 (Thbs4) expression in dorsal root ganglion (DRG) on peripheral nerve injury repair and regeneration, as well as to elucidate the underlying molecular mechanisms. Methods: A sciatic nerve transection model in rat was established to analyze Thbs4 expression and localization in DRG tissues after injury. Both siRNA and adeno-associated virus (AAV) were used to knockdown or overexpress Thbs4. The effects of knockdown and overexpression of Thbs4 on axon growth were assessed using immunofluorescence staining. The roles of Thbs4 in peripheral nerve injury repair and regeneration were determined using behavioral assays, electrophysiological recordings, and transmission electron microscopy. Results: Thbs4 was primarily localized in the cell membrane and cytoplasm of DRG neurons but was also found in the intercellular spaces. In vitro experiments demonstrated that Thbs4 overexpression promoted axonal regeneration and reduced neuronal apoptosis. They also showed that Thbs4 overexpression accelerated sciatic nerve regeneration and enhanced the recovery of motor and sensory functions. Conversely, Thbs4 knockdown had the opposite effects. This study also showed that the knockdown or overexpression of Thbs4 significantly altered the expression of NF-κB and ERK signaling pathways, suggesting their involvement in peripheral nerve repair and regeneration. Conclusions: Thbs4 expression in DRG tissues is significantly altered following sciatic nerve injury. The NF-κB and ERK may be involved in regulating the repair and regeneration of the peripheral nerve by Thbs4.