Dysregulated miR-29a-3p/PMP22 Modulates Schwann Cell Proliferation and Migration During Peripheral Nerve Regeneration

Shen, Yinying; Cheng, Zhangchun; Chen, Sailing; Zhang, Yunsong; Chen, Qi; Yi, Sheng

doi:10.1007/s12035-021-02589-2

Cited by 15 publications

(8 citation statements)

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“…The other SD rats were used for examining the in vivo effect of miR-195-5p. miR-195-5p agomir or agomir control was applied to rat sciatic nerves as described previously with modifications ( Yi et al, 2017 ; Shen et al, 2022 ). Briefly, the in vivo effect of miR-195-5p on rat sciatic nerve was evaluated by distributing 5 nmol agomir or agomir control (RiboBio, Guangzhou, Guangdong, China) dissolved in 5 μL saline, mixing with Matrigel matrix basement membrane (Corning, NY, USA) at a volume ratio of 1: 1 and injecting 2 days prior to and immediately following crush injury in the epineurium of rat sciatic nerve.…”

Section: Methodsmentioning

confidence: 99%

“…Furthermore, a large number of miRNAs exhibit differential expression post-PNI ( Yu et al, 2015 ; Gu et al, 2022 ). Current evidence suggests that differentially expressed miRNAs influence Schwann cell behaviors, such as myelinophagy, proliferation, migration and myelination, with potential effects on peripheral nerve repair and regeneration ( Yi et al, 2017 ; Wang et al, 2019 ; Shen et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

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Regulation of Schwann cell proliferation and migration via miR-195-5p-induced Crebl2 downregulation upon peripheral nerve damage

Zhang

et al. 2023

Front. Cell. Neurosci.

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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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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Regulation of Schwann cell proliferation and migration via miR-195-5p-induced Crebl2 downregulation upon peripheral nerve damage

Zhang

et al. 2023

Front. Cell. Neurosci.

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“…We have previously demonstrated that down‐regulated miR‐1 after peripheral nerve injury up‐regulates brain‐derived neurotrophic factor and promotes Schwann cell proliferation and migration (Yi et al, 2016). On the contrast, up‐regulated miR‐29a‐3p post‐nerve injury inhibits Schwann cell proliferation and migration by targeting and negatively regulating peripheral myelin protein 22 (Shen et al, 2022). Therefore, mRNA and miRNA sequencing were jointly performed from cultured SN and DRG Schwann cells.…”

Section: Discussionmentioning

confidence: 99%

“…Data are presented as mean ± SEM (n = 4 of independent cell culture preparations; *p-value < 0.05, ordinary one-way ANOVA; q = 2.804, df = 9, adjusted pvalue = 0.0369 for versus miR-140 mimic and q = 5.237, df = 9, adjusted p-value = 0.0010 for mimic control versus miR-200 mimic; q = 0.6842, df = 9, adjusted p-value = 0.7262 for inhibitor control versus miR-140 inhibitor and q = 0.5154, df = 9, adjusted p-value = 0.8294 for inhibitor control versus miR-200 inhibitor). regulating peripheral myelin protein 22 (Shen et al, 2022). Therefore, (Viader et al, 2011).…”

Section: Enhanced Migration Capacity Of Drg Schwann Cells Indicates Thatmentioning

confidence: 99%

miR‐140 and miR‐200 regulate the migratory heterogeneity of location‐specific Schwann cell population

Chen

Miao

et al. 2023

Journal of Neurochemistry

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Schwann cells are functional cells in nerve regeneration and are commonly used as seed cells in tissue engineering. Enhanced Schwann cell migration capacity improves recovery effects, and thus, the identification of Schwann cells with greater migration ability is of great importance. In the present study, we examined the biological activities of Schwann cells collected from rat sciatic nerves (SN) and dorsal root ganglia (DRG). Observations from transwell migration assay and wound healing assay demonstrate that DRG Schwann cells migrate at a faster speed as compared with SN Schwann cells. Sequencing and bioinformatics suggest that differentially expressed genes between SN and DRG Schwann cells are associated with cell motility and migration. miR‐140 and miR‐200, two microRNAs (miRNAs) that are highly expressed in SN Schwann cells negatively influence Schwann cell migration and thus may be key regulators of Schwann cell phenotype. Igsf10, Plxna2, and Lcp1 are screened as candidate downstream targets of miR‐140 and miR‐200 based on bioinformatic analysis and their expression correlation with miRNAs. Our comparative analysis displays the unique characteristics of Schwann cells in different anatomical localizations and demonstrates that DRG Schwann cells are suitable seed cells for tissue engineering and regenerative medicine.image

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“…The upregulated miR-sc14 acts on fibroblast growth factor receptor 2 and miR-3099 acts on multiple targets including Aqp4, St8sia2, Tnfsf15 and Zbtb16 to promote the proliferation and migration of SCs 62 , 63 . Mir-29a-3p inhibits proliferation and migration of SCs by negatively regulating peripheral myelin protein 22 (PMP22), which is closely correlated with myelin sheath formation 64 .…”

Section: Non-coding Rnas In Peripheral Nerve Regenerationmentioning

confidence: 99%

Role of Non-coding RNAs in Axon Regeneration after Peripheral Nerve Injury

Liu¹,

Li²,

Jia³

et al. 2022

Int. J. Biol. Sci.

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Peripheral nerve injury (PNI) may lead to disability and neuropathic pain, which constitutes a substantial economic burden to patients and society. It was found that the peripheral nervous system (PNS) has the ability to regenerate after injury due to a permissive microenvironment mainly provided by Schwann cells (SCs) and the intrinsic growth capacity of neurons; however, the results of injury repair are not always satisfactory. Effective, long-distance axon regeneration after PNI is achieved by precise regulation of gene expression. Numerous studies have shown that in the process of peripheral nerve damage and repair, differential expression of non-coding RNAs (ncRNAs) significantly affects axon regeneration, especially expression of microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs). In the present article, we review the cellular and molecular mechanisms of axon regeneration after PNI, and analyze the roles of these ncRNAs in nerve repair. In addition, we discuss the characteristics and functions of these ncRNAs. Finally, we provide a thorough perspective on the functional mechanisms of ncRNAs in nervous injury repair, and explore the potential these ncRNAs offer as targets of nerve injury treatment.

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Dysregulated miR-29a-3p/PMP22 Modulates Schwann Cell Proliferation and Migration During Peripheral Nerve Regeneration

Cited by 15 publications

References 50 publications

Regulation of Schwann cell proliferation and migration via miR-195-5p-induced Crebl2 downregulation upon peripheral nerve damage

Regulation of Schwann cell proliferation and migration via miR-195-5p-induced Crebl2 downregulation upon peripheral nerve damage

miR‐140 and miR‐200 regulate the migratory heterogeneity of location‐specific Schwann cell population

Role of Non-coding RNAs in Axon Regeneration after Peripheral Nerve Injury

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