Matrix metalloproteinase 7 promoted Schwann cell migration and myelination after rat sciatic nerve injury

Wang, Hongkui; Zhang, Ping; Yu, Jun; Zhang, Fuchao; Dai, Wenzhao; Yi, Sheng

doi:10.1186/s13041-019-0516-6

Cited by 25 publications

(18 citation statements)

References 33 publications

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“…Therefore, many studies have attempted to evaluate the feasibility of enhancing peripheral nerve regeneration by promoting SC migration. It has been shown that matrix metalloproteinase 7 (MMP-7) promotes axonal regeneration and remyelination by enhancing SC migration after sciatic nerve injury in rats (Wang H. et al, 2019). In addition, enhancing SC migration using concentration gradients of laminin-derived peptides has been shown to support axonal regeneration over a large nerve gap, further confirming the role of SC migration in axonal regeneration (Motta et al, 2019).…”

Section: Discussionmentioning

confidence: 93%

Epothilone B Facilitates Peripheral Nerve Regeneration by Promoting Autophagy and Migration in Schwann Cells

Zhou

Gao

et al. 2020

Front. Cell. Neurosci.

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The search for drugs that can facilitate axonal regeneration and elongation following peripheral nerve injury has been an area of increasing interest in recent years. Epothilone B (EpoB) is an FDA-approved antineoplastic agent, which shows the capacity to induce α-tubulin polymerization and to improve the stability of microtubules. Recently, it has been increasingly recognized that EpoB has a regenerative effect in the central nervous system. However, the information currently available regarding the potential therapeutic effect of EpoB on peripheral nerve regeneration is limited. Here, we used a rat sciatic crush injury model system to determine that EpoB strikingly improved axonal regeneration and recovery of function. Also, EpoB (1 nM) did not result in significant apoptosis in Schwann cells (SCs) and showed little effect on their viability either. Interestingly, EpoB (1 nM) significantly enhanced migration in SCs, which was inhibited by autophagy inhibitors 3-methyladenine (3-MA). Since PI3K/Akt signaling has been implicated in regulating autophagy, we further examined the involvement of PI3K/Akt in the process of EpoB-induced SC migration. We found that EpoB (1 nM) significantly inhibited phosphorylation of PI3K and Akt in SCs. Further studies showed that both EpoB-enhanced migration and autophagy were increased/inhibited by inhibition/activation of PI3K/Akt signaling with LY294002 or IGF-1. In conclusion, EpoB can promote axonal regeneration following peripheral nerve injury by enhancing the migration of SCs, with this activity being controlled by PI3K/Akt signaling-mediated autophagy in SCs. This underscores the potential therapeutic value of EpoB in enhancing regeneration and functional recovery in cases of peripheral nerve injury.

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Section: Discussionmentioning

confidence: 93%

Epothilone B Facilitates Peripheral Nerve Regeneration by Promoting Autophagy and Migration in Schwann Cells

Zhou

Gao

et al. 2020

Front. Cell. Neurosci.

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“…Furthermore, according to microarray data ( Figure 1 K), critical transcriptional factors and proteins such as Arfgef2 , Arhgef2 , Srf , Fos , Cdk6 , Bdkrb1 , Gsn , Abca1 , which are reported to be related to RhoA/YAP/TAZ signaling, were upregulated for SCs seeded on stiff substrates [ 40 , 41 , 42 , 43 , 44 , 45 ]. Meanwhile, SC regenerative genes were upregulated for SCs seeded on soft substrates, such as EGF , Atf3 , Cspg4 (Ng2) , Id2 , Mmp7 , and Wnt signaling [ 46 , 47 , 48 , 49 ].…”

Section: Resultsmentioning

confidence: 99%

Cell Shape and Matrix Stiffness Impact Schwann Cell Plasticity via YAP/TAZ and Rho GTPases

Orkwis

Harris

2021

IJMS

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Schwann cells (SCs) are a highly plastic cell type capable of undergoing phenotypic changes following injury or disease. SCs are able to upregulate genes associated with nerve regeneration and ultimately achieve functional recovery. During the regeneration process, the extracellular matrix (ECM) and cell morphology play a cooperative, critical role in regulating SCs, and therefore highly impact nerve regeneration outcomes. However, the roles of the ECM and mechanotransduction relating to SC phenotype are largely unknown. Here, we describe the role that matrix stiffness and cell morphology play in SC phenotype specification via known mechanotransducers YAP/TAZ and RhoA. Using engineered microenvironments to precisely control ECM stiffness, cell shape, and cell spreading, we show that ECM stiffness and SC spreading downregulated SC regenerative associated proteins by the activation of RhoA and YAP/TAZ. Additionally, cell elongation promoted a distinct SC regenerative capacity by the upregulation of Rac1/MKK7/JNK, both necessary for the ECM and morphology changes found during nerve regeneration. These results confirm the role of ECM signaling in peripheral nerve regeneration as well as provide insight to the design of future biomaterials and cellular therapies for peripheral nerve regeneration.

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“…In the process of nerve regeneration, SCs can secrete a large number of growth factors to promote axon growth and myelin formation, which play a key role in peripheral nerve regeneration (24,25). Oxidative stress can affect DNA synthesis and mitochondrial function, and completely destroy cell integrity.…”

Section: Discussionmentioning

confidence: 99%

Effects of Salvia miltiorrhiza injection on apoptosis of Schwann cells induced by hydrogen peroxide

et al. 2021

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Background: Salvia miltiorrhiza is a traditional Chinese medicine with remarkable antioxidant, antibacterial, and anticoagulant properties. In the present study, we investigated the effects of Salvia miltiorrhiza injection in protecting Schwann cells (SCs) from hydrogen peroxide (H 2 O 2 )-induced cell apoptosis.Methods: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and immunofluorescence staining were used to detect the establishment of the SC apoptosis model induced by H 2 O 2 . The effect of Salvia miltiorrhiza injection on injured cell morphology was observed, and the effect on cell apoptosis was determined by Annexin V-fluorescein isothiocyanate (FITC) apoptosis detection kit and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. Western blotting analysis was used to detect the effect of Salvia miltiorrhiza injection on apoptosis-related protein expression. Results:The results of the MTT assay showed that cell activity significantly decreased after treatment with 1 mM H 2 O 2 , but different concentrations of Salvia miltiorrhiza injection could improve cell activity at different degrees. The number of cells increased significantly after treatment with Salvia miltiorrhiza injection. Annexin V-FITC/PI double staining and TUNEL results revealed that Salvia miltiorrhiza injection could significantly reduce apoptosis induced by H 2 O 2 . Western blotting analysis showed that the expression of Bcl-2 was significantly upregulated, while the expression level of Bax was significantly downregulated.Conclusions: Salvia miltiorrhiza injection can protect SCs from H 2 O 2 -induced cell apoptosis, and has potential therapeutic effects in neurological disease.

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Matrix metalloproteinase 7 promoted Schwann cell migration and myelination after rat sciatic nerve injury

Cited by 25 publications

References 33 publications

Epothilone B Facilitates Peripheral Nerve Regeneration by Promoting Autophagy and Migration in Schwann Cells

Epothilone B Facilitates Peripheral Nerve Regeneration by Promoting Autophagy and Migration in Schwann Cells

Cell Shape and Matrix Stiffness Impact Schwann Cell Plasticity via YAP/TAZ and Rho GTPases

Effects of Salvia miltiorrhiza injection on apoptosis of Schwann cells induced by hydrogen peroxide

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