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MiR-7 inhibited peripheral nerve injury repair by affecting neural stem cells migration and proliferation through cdc42.

ABSTRACT: Objective Neural stem cells play an important role in the recovery and regeneration of peripheral nerve injury, and the microRNA-7 (miR-7) regulates differentiation of neural stem cells. This study aimed to explore the role of miR-7 in neural stem cells homing and proliferation and its influence on peripheral nerve injury repair. Methods The mice model of peripheral nerve injury was created by segmental sciatic nerve defect (sciatic nerve injury), and neural stem cells treatment was performed with a gelatin hydrogel conduit containing neural stem cells inserted into the sciatic nerve injury mice. The Sciatic Function Index was used to quantify sciatic nerve functional recovery in the mice. The messenger RNA and protein expression were detected by reverse transcription polymerase chain reaction and Western blot, respectively. Luciferase reporter assay was used to confirm the binding between miR-7 and the 3'UTR of cell division cycle protein 42 (cdc42). The neural stem cells migration and proliferation were analyzed by transwell assay and a Cell-LightTM EdU DNA Cell Proliferation kit, respectively. Results Neural stem cells treatment significantly promoted nerve repair in sciatic nerve injury mice. MiR-7 expression was decreased in sciatic nerve injury mice with neural stem cells treatment, and miR-7 mimic transfected into neural stem cells suppressed migration and proliferation, while miR-7 inhibitor promoted migration and proliferation. The expression level and effect of cdc42 on neural stem cells migration and proliferation were opposite to miR-7, and the luciferase reporter assay proved that cdc42 was a target of miR-7. Using co-transfection into neural stem cells, we found pcDNA3.1-cdc42 and si-cdc42 could reverse respectively the role of miR-7 mimic and miR-7 inhibitor on neural stem cells migration and proliferation. In addition, miR-7 mimic-transfected neural stem cells could abolish the protective role of neural stem cells on peripheral nerve injury. Conclusion MiR-7 inhibited peripheral nerve injury repair by affecting neural stem cells migration and proliferation through cdc42.

SUBMITTER: Zhou N

PROVIDER: S-EPMC5912295 | biostudies-literature | 2018 Jan-Dec

REPOSITORIES: biostudies-literature

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MiR-7 inhibited peripheral nerve injury repair by affecting neural stem cells migration and proliferation through cdc42.

Zhou Nan N Hao Shuang S Huang Zongqiang Z Wang Weiwei W Yan Penghui P Zhou Wei W Zhu Qihang Q Liu Xiaokang X

Molecular pain 20180101

Objective Neural stem cells play an important role in the recovery and regeneration of peripheral nerve injury, and the microRNA-7 (miR-7) regulates differentiation of neural stem cells. This study aimed to explore the role of miR-7 in neural stem cells homing and proliferation and its influence on peripheral nerve injury repair. Methods The mice model of peripheral nerve injury was created by segmental sciatic nerve defect (sciatic nerve injury), and neural stem cells treatment was performed wi ...[more]

PMID: 29663842

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Project description:After peripheral nerve injury, intraperitoneal injection of folic acid improves axon quantity, increases axon density and improves electromyography results. However, the mechanisms for this remain unclear. This study explored whether folic acid promotes peripheral nerve injury repair by affecting Schwann cell function. Primary Schwann cells were obtained from rats by in vitro separation and culture. Cell proliferation, assayed using the Cell Counting Kit-8 assay, was higher in cells cultured for 72 hours with 100 mg/L folic acid compared with the control group. Cell proliferation was also higher in the 50, 100, 150, and 200 mg/L folic acid groups compared with the control group after culture for 96 hours. Proliferation was markedly higher in the 100 mg/L folic acid group compared with the 50 mg/L folic acid group and the 40 ng/L nerve growth factor group. In Transwell assays, the number of migrated Schwann cells dramatically increased after culture with 100 and 150 mg/L folic acid compared with the control group. In nerve growth factor enzyme-linked immunosorbent assays, treatment of Schwann cell cultures with 50, 100, and 150 mg/L folic acid increased levels of nerve growth factor in the culture medium compared with the control group at 3 days. The nerve growth factor concentration of Schwann cell cultures treated with 100 mg/L folic acid group was remarkably higher than that in the 50 and 150 mg/L folic acid groups at 3 days. Nerve growth factor concentration in the 10, 50, and 100 mg/L folic acid groups was higher than that in the control group at 7 days. The nerve growth factor concentration in the 50 mg/L folic acid group was remarkably higher than that in the 10 and 100 mg/L folic acid groups at 7 days. In vivo, 80 μg/kg folic acid was intraperitoneally administrated for 7 consecutive days after sciatic nerve injury. Immunohistochemical staining showed that the number of Schwann cells in the folic acid group was greater than that in the control group. We suggest that folic acid may play a role in improving the repair of peripheral nerve injury by promoting the proliferation and migration of Schwann cells and the secretion of nerve growth factors.

Project description:BackgroundSchwann cells acquire a repair phenotype upon peripheral nerve injury (PNI), generating an optimal microenvironment that drives nerve repair. Multiple microRNAs (miRNAs) show differential expression in the damaged peripheral nerve, with critical regulatory functions in Schwann cell features. This study examined the time-dependent expression of miR-195-5p following PNI and demonstrated a marked dysregulation of miR-195-5p in the damaged sciatic nerve.MethodsCCK-8 and EdU assays were used to evaluate the effect of miR-195-5 on Schwann cell viability and proliferation. Schwann cell migration was tested using Transwell and wound healing assays. The miR-195-5p agomir injection experiment was used to evaluate the function of miR-195-5p in vivo. The potential regulators and effects of miR-195-5p were identified through bioinformatics evaluation. The relationship between miR-195-5p and its target was tested using double fluorescence reporter gene analysis.ResultsIn Schwann cells, high levels of miR-195-5p decreased viability and proliferation, while suppressed levels had the opposite effects. However, elevated miR-195-5p promoted Schwann cell migration determined by the Transwell and wound healing assays. In vivo injection of miR-195-5p agomir into rat sciatic nerves promote axon elongation after peripheral nerve injury by affecting Schwann cell distribution and myelin preservation. Bioinformatic assessment further revealed potential regulators and effectors for miR-195-5p, which were utilized to build a miR-195-5p-centered competing endogenous RNA network. Furthermore, miR-195-5p directly targeted cAMP response element binding protein-like 2 (Crebl2) mRNA via its 3'-untranslated region (3'-UTR) and downregulated Crebl2. Mechanistically, miR-195-5p modulated Schwann cell functions by repressing Crebl2.ConclusionThe above findings suggested a vital role for miR-195-5p/Crebl2 in the regulation of Schwann cell phenotype after sciatic nerve damage, which may contribute to peripheral nerve regeneration.

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MiR-7 inhibited peripheral nerve injury repair by affecting neural stem cells migration and proliferation through cdc42.

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MiR-7 inhibited peripheral nerve injury repair by affecting neural stem cells migration and proliferation through cdc42.

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