TGF-β1/P-Snail1-NGF signaling axis mediates the repair of peripheral nerve injury in rats

In the repair process of peripheral nerve injury, Schwann cells rapidly migrate to the injury site, where they form a neural sheath and secrete nerve growth factor (NGF) to facilitate nerve regeneration. Enhancing Schwann cell migration and boosting NGF secretion from Schwann cell are thus critical for effective nerve repair. Our study demonstrates that in the presence of transforming growth factor-beta 1 (TGF-β1), NGF secretion by Schwann cells is significantly upregulated in a concentration- and time-dependent manner. Importantly, we reveal that TGF-β1 through the TGF-β1/Smad3 signaling pathway promotes the phosphorylation of Snail1 as transcription factor. Snail1 phosphorylation has been shown to enhance its binding affinity to the NGF promoter, thereby directly upregulating NGF transcription. This mechanism is critical for promoting peripheral nerve regeneration and repair processes in response to injury.The use of Snail1 phosphorylation inhibitors, such as LiCl, has demonstrated a significant reduction in NGF expression, highlighting the necessity of Snail1 phosphorylation for the upregulation of NGF transcription.Moreover,the results also show that TGF-β1 promotes the expression of NGF and contributes to the repair of sciatic nerve damage and functional recovery in vivo.Collectively, our findings elucidate the TGF-β1/Smad3-p-Snail1-NGF signaling axis as a key regulator of peripheral nerve injury repair.