miR-129 controls axonal regeneration via regulating insulin-like growth factor-1 in peripheral nerve injury

Abstract

The microenvironment of peripheral nerve regeneration consists of multiple neurotrophic factors, adhesion molecules, and extracellular matrix molecules, secreted by unique glial cells in the peripheral nerve system (PNS)-Schwann cell (SCs). Following peripheral nerve injury (PNI), local IGF-1 production is upregulated in SCs and denervated muscle during axonal sprouting and regeneration. Regulation of IGF-1/IGF-1R signaling is considered as a potentially targeted therapy of PNI. We previously identified a group of novel miRNAs in proximal nerve following rat sciatic nerve transection. The present work focused on the role of miR-129 in regulation of IGF-1 signaling after sciatic nerve injury. The temporal change profile of the miR-129 expression was negatively correlated with the IGF-1 expression in proximal nerve stump and dorsal root ganglion (DRG) following sciatic nerve transection. An increased expression of miR-129 inhibited proliferation and migration of SCs, and axonal outgrowth of DRG neurons, which was inversely promoted by silencing of the miR-129 expression. The IGF-1 was identified as one of the multiple target genes of miR-129, which exerted negative regulation of IGF-1 by translational suppression. Moreover, knockdown of IGF-1 attenuated the promoting effects of miR-129 inhibitor on proliferation and migration of SCs, and neurite outgrowth of DRG neurons. Overall, our data indicated that miR-129 own the potential to regulate the proliferation and migration of SCs by targeting IGF-1, providing further insight into the regulatory role of miRNAs in peripheral nerve regeneration. The present work not only provides new insight into miR-129 regulation of peripheral nerve regeneration by robust phenotypic modulation of neural cells, but also opens a novel therapeutic window for PNI by mediating IGF-1 production. Our results may provide further experimental basis for translation of the molecular therapy into the clinic.

Differential Circular RNA Expression Profiles Following Spinal Cord Injury in Rats: A Temporal and Experimental Analysis

“…ncRNAs are categorized into many different types, including small nuclear RNAs (snRNAs), small nucleolar RNAs (snoRNAs), transfer RNAs (tRNAs), ribosomal RNAs (rRNAs), PIWI (P-element-induced wimpy testis)-interacting RNAs (piRNAs), miRNAs, long ncRNAs (lncRNAs), and circRNAs. Previously, we found that the lncRNA TNXA-PS1 modulates Schwann cells (Yao et al, 2018), where miR-129 controls axonal regeneration during peripheral nerve injury (Zhu et al, 2018).…”

Electroacupuncture Promoted Nerve Repair After Peripheral Nerve Injury by Regulating miR-1b and Its Target Brain-Derived Neurotrophic Factor

“…Although EA treatment has been convinced to be helpful for nerve repair after PNI ( Inoue et al, 2003 ; Pan et al, 2019 ), the mechanism is not very clear. Studies showed that the expression of multiple miRNAs has changed such as miR-129 ( Zhu et al, 2018 ) and miR-195 ( Shi et al, 2013 ) after PNI. It has been reported that EA enhanced neurobehavioral functional recovery against ischemic stroke through targeting of SOX2-mediated axonal regeneration by miR-132 ( Cui et al, 2017 ; Zhao X. et al, 2018 ).…”

Identification of adhesion‑associated DNA methylation patterns in the peripheral nervous system

“…Pain reduction in patients with PNI is an important area of focus in medicine. Previous studies have demonstrated that Schwann cells serve an important role in promoting axonal regeneration, myelin repair and functional recovery in neuroregeneration (9)(10)(11).…”