Abstract:
After peripheral nerve injury (PNI), the long-term healing process at the injury site involves a progressive accumulation of collagen fibers and the development of localized scar tissue. Excessive formation of scar tissue within nerves hinders the process of nerve repair. In this study, we demonstrate that scar formation following nerve injury induces alterations in the local physical microenvironment, specifically an increase in nerve stiffness. Recent research has indicated heightened expression of Piezo1 in Schwann cells (SCs). Our findings also indicate Piezo1 expression in SCs and its association with suppressed proliferation and migration. Transcriptomic data suggests that activation of Piezo1 results in elevated expression of senescence-associated genes. GO enrichment analysis reveals upregulation of the TGF-β pathway. Overall, our study highlights the potential for Piezo1-induced signaling to regulate SC senescence and its potential significance in the pathophysiology of fibrotic scar formation surrounding peripheral nerves.
摘要:
周围神经损伤(PNI)后,损伤部位的长期愈合过程涉及胶原纤维的逐渐积累和局部瘢痕组织的发展。神经内瘢痕组织的过度形成阻碍了神经修复过程。在这项研究中,我们证明了神经损伤后的瘢痕形成会引起局部物理微环境的改变,特别是神经僵硬的增加。最近的研究表明Piezo1在施万细胞(SC)中的表达增强。我们的发现还表明Piezo1在SCs中的表达及其与抑制增殖和迁移的关联。转录组数据表明Piezo1的激活导致衰老相关基因的表达升高。GO富集分析揭示了TGF-β途径的上调。总的来说,我们的研究强调了Piezo1诱导的信号调节SC衰老的潜力及其在周围神经周围纤维化瘢痕形成的病理生理学中的潜在意义.