scholarly journals SPP1 Promotes Schwann Cell Proliferation and Survival through PKCα by Binding with CD44 and αvβ3 after Peripheral Nerve Injury

2020 ◽  
Author(s):  
Jiang-Bo Wang ◽  
Zhan Zhang ◽  
Jian-Nan Li ◽  
Tuo Yang ◽  
Shuang Du ◽  
...  

Abstract Background: Schwann cells (SCs) play a crucial role in Wallerian degeneration after peripheral nerve injury. The expression of genes in SCs undergo a series of changes, which greatly affect the proliferation and apoptosis of SCs as well as the fate of peripheral nerve regeneration. However, how do these genes regulate the proliferation and apoptosis of SCs remains unclear. Results: SPP1 and PKCα were found upregulated after human median peripheral nerve injury, which promoted SCs proliferation and survival. The promoted proliferation and inhibited apoptosis by SPP1 were blocked after the treatment of PKCα antagonist Gö6976. Whereas, the inhibited proliferation and enhanced apoptosis induced by silence of SPP1 could be rescued by the activation of PKCα, which suggested that SPP1 functioned through PKCα. Moreover, both CD44 and αvβ3 were found expressed in SCs and increased after peripheral nerve injury. Silence of CD44 or β3 alleviated the increased proliferation and inhibited apoptosis induced by recombinant osteopontin, suggesting the function of SPP1 on SCs were dependent on CD44 and β3. Conclusion: These results suggested that SPP1 promoted proliferation and inhibited apoptosis of SCs through PKCα signaling pathway by binding with CD44 and αvβ3. This study provides a potential therapeutic target for improving peripheral nerve recovery.

Author(s):  
Zhiwen Yan ◽  
Cheng Chen ◽  
Gonzalo Rosso ◽  
Yun Qian ◽  
Cunyi Fan

Peripheral nerve tissues possess the ability to regenerate within artificial nerve scaffolds, however, despite the advance of biomaterials that support nerve regeneration, the functional nerve recovery remains unsatisfactory. Importantly, the incorporation of two-dimensional nanomaterials has shown to significantly improve the therapeutic effect of conventional nerve scaffolds. In this review, we examine whether two-dimensional nanomaterials facilitate angiogenesis and thereby promote peripheral nerve regeneration. First, we summarize the major events occurring after peripheral nerve injury. Second, we discuss that the application of two-dimensional nanomaterials for peripheral nerve regeneration strategies by facilitating the formation of new vessels. Then, we analyze the mechanism that the newly-formed capillaries directionally and metabolically support neuronal regeneration. Finally, we prospect that the two-dimensional nanomaterials should be a potential solution to long range peripheral nerve defect. To further enhance the therapeutic effects of two-dimensional nanomaterial, strategies which help remedy the energy deficiency after peripheral nerve injury could be a viable solution.


Brain ◽  
2008 ◽  
Vol 131 (10) ◽  
pp. 2620-2631 ◽  
Author(s):  
Rubèn López-Vales ◽  
Xavier Navarro ◽  
Takao Shimizu ◽  
Constantinos Baskakis ◽  
George Kokotos ◽  
...  

2021 ◽  
Vol 9 ◽  
Author(s):  
Shixian Dong ◽  
Sijia Feng ◽  
Yuzhou Chen ◽  
Mo Chen ◽  
Yimeng Yang ◽  
...  

Peripheral nerve injury gives rise to devastating conditions including neural dysfunction, unbearable pain and even paralysis. The therapeutic effect of current treatment for peripheral nerve injury is unsatisfactory, resulting in slow nerve regeneration and incomplete recovery of neural function. In this study, nerve suture combined with ADSCs injection was adopted in rat model of sciatic nerve injury. Under real-time visualization of the injected cells with the guidance of NIR-II fluorescence imaging in vivo, a spatio-temporal map displaying cell migration from the proximal injection site (0 day post-injection) of the nerve to the sutured site (7 days post-injection), and then to the distal section (14 days post-injection) was demonstrated. Furthermore, the results of electromyography and mechanical pain threshold indicated nerve regeneration and functional recovery after the combined therapy. Therefore, in the current study, the observed ADSCs migration in vivo, electrophysiological examination results and pathological changes all provided robust evidence for the efficacy of the applied treatment. Our approach of nerve suture combined with ADSCs injection in treating peripheral nerve injury under real-time NIR-II imaging monitoring in vivo added novel insights into the treatment for peripheral nerve injury, thus further enhancing in-depth understanding of peripheral nerve regeneration and the mechanism behind.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ying Zou ◽  
Jiaqi Zhang ◽  
Jiawei Xu ◽  
Lanya Fu ◽  
Yizhou Xu ◽  
...  

Abstract Background Silent information regulator 6 (SIRT6) is a mammalian homolog of the nicotinamide adenine dinucleotide (NAD)-dependent deacetylase sirtuin family. Prior evidences suggested that the anti-inflammatory function of SIRT6 after spinal cord and brain injury, and it plays a crucial role in macrophages polarization of adipose tissue and skin. However, the role of SIRT6 in macrophages involved peripheral nerve injury is still unknown. Given the prominent role of macrophages in peripheral nerve recovery, we aim to investigate the role of SIRT6 in the regulation of phenotypes shift and functions in macrophages after peripheral nerve injury. Results In the present study, we first identified a significant increase of SIRT6 expression during nerve degeneration and macrophages phagocytosis. Next, we found nerve recovery was delayed after SIRT6 silencing by injected shRNA lentivirus into the crushed sciatic nerve, which exhibited a reduced expression of myelin-related proteins (e.g., MAG and MBP), severer myoatrophy of target muscles, and inferior nerve conduction compared to the shRNA control injected mice. In vitro, we found that SIRT6 inhibition by being treated with a selective inhibitor OSS_128167 or lentivirus transfection impairs migration and phagocytosis capacity of bone marrow-derived macrophages (BMDM). In addition, SIRT6 expression was discovered to be reduced after M1 polarization, but SIRT6 was enhanced after M2 polarization in the monocyte-macrophage cell line RAW264.7 and BMDM. Moreover, SIRT6 inhibition increased M1 macrophage polarization with a concomitant decrease in M2 polarization both in RAW264.7 and BMDM via activating NF-κB and TNF-α expression, and SIRT6 activation by UBCS039 treatment could shift the macrophages from M1 to M2 phenotype. Conclusion Our findings indicate that SIRT6 inhibition impairs peripheral nerve repair through suppressing the migration, phagocytosis, and M2 polarization of macrophages. Therefore, SIRT6 may become a favorable therapeutic target for peripheral nerve injury.


2021 ◽  
Vol 16 (6) ◽  
pp. 1078
Author(s):  
Jiasong Guo ◽  
Lixia Li ◽  
Yizhou Xu ◽  
Xianghai Wang ◽  
Jingmin Liu ◽  
...  

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