非特异性下腰痛中治疗作用靶点--信号素Sema3A的研究进展

Current advances in research of semaphorin 3A:a potential target for the treatment of nospecific low back pain

神经长入和炎症反应是非特异痛性椎间盘最显著的病理改变。信号素Sema3A(Semaphorin3A)是一类跨膜蛋白家族,通过与NRP-1/plexinA受体复合,调控Sema3A-NRP-1-plexinA信号通路,在神经元发育、损伤与修复等过程中发挥重要的化学趋化及导向作用。近来研究发现Sema3A抑制DRG(dorsal root ganglion)神经元轴突生长,退变椎间盘中Sema3A显著下降,诱导外围神经长入纤维环内层及髓核。此外,Sema3A可抑制KLF5(Krüppel-like factor 5)介导的炎性反应,拮抗血管内皮生长因子的活性,导致新生血管受阻,抑制血管内皮细胞的生长和发展。因此,通过Sema3A调节退变椎间盘病理性神经血管长入及炎症反应成为一个新的治疗方向。

Nonspecific low back pain is closely associated with afferent nerve ingrowth into degenerated IVDs and increasing the inflammatory response.Members of the class 3 semaphorins signal their response through two prominent receptors;the NRP(Neuropilin-1)and the Plexin A.Sema3A(Semaphorin3A)is primarily known for their role in modulating neuronal survival as well as neurite outgrowth and guidance via regulation of Sema3A-NRP-1-plexinA signal pathway.Also,sema3A is shown to be conductive to innervate the inner painful degenerated IVDs(Intervertebral discs).Furthermore,sema3A is thought to act as a barrier to endothelial cells survival and migration on vascular endothelial growth factor(VEGF)and inhibition of KLF5-induced(Krüppel-like factor 5)inflammatory mediators within degenerated IVDs.Therefore,Sema3A produce a new perspective of dual-action therapeutic agent for attenuating the regulator of innervation and angiogenesis into degenerated IVDs and inhibition of KLF5-induced inflammation.