Extrinsic and Intrinsic Regulation of Axon Regeneration by MicroRNAs after Spinal Cord Injury

Li, Ping; Teng, Zhao‐Qian; Liu, Chang‐Mei

doi:10.1155/2016/1279051

Cited by 30 publications

(23 citation statements)

References 115 publications

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“…Data were compared by one-way or two-way ANOVA. *p < 0.05 vs sham group or NC mimic versatile functions in key events such as oligodendrocyte development, axonal regeneration, and remyelination [7,26]. In the present research, we validated the potent functions of miR-29a/199B in neurologic and locomotor functional recovery in a rat model with the involvement of downregulation of RGMA and the suppression of the STAT3 signaling pathway.…”

Section: Discussionsupporting

confidence: 58%

Promoting functions of microRNA-29a/199B in neurological recovery in rats with spinal cord injury through inhibition of the RGMA/STAT3 axis

Yang

Sun

2020

J Orthop Surg Res

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Background The prognostic and therapeutic potential of microRNAs (miRNAs) in spinal cord injury (SCI) has aroused increasing concerns. This study aims to research the functions of miR-29a/199B in the neurological function recovery after SCI and the mechanical mechanism. Methods A rat model with SCI was induced with sham-operated ones as control. The locomotor function and coordination of rat hindlimbs were determined by a Basso, Beattie, and Bresnahan (BBB) locomotor rating scale and a ladder-climbing test, respectively. Expression of a neurofilament protein NF-200 and synaptophysin in gray matter of rats was determined to evaluate neuronal recovery in a cellular perspective. Binding relationships between miR-29a/199B with RGMA were predicted and validated using luciferase assays. Altered expression of miR-29a/199B and RGMA was introduced to explore their functions in rat neurological functions. The protein level and phosphorylation of STAT3 in gray matter were measured by western blot analysis. Results miR-29a and miR-199B were poorly expressed, while RGMA was abundantly expressed in gray matter at injury sites. Either miR-29a or miR-199B could bind to RGMA. Overexpression of miR-29a/199B or silencing of RGMA led to an increase in BBB locomotor scores, hindlimb coordination ability, and the expression of NF-200 and synaptophysin in gray matter. Further inhibition in miR-29a/199B blocked the promoting roles of RGMA silencing in neurological recovery. Upregulation of miR-29a/199B or downregulation of RGMA suppressed the phosphorylation of STAT3. Conclusion This study evidenced that miR-29a and miR-199B negatively regulated RGMA to suppress STAT3 phosphorylation, therefore promoting the neurological function recovery in rats following SCI.

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Section: Discussionsupporting

confidence: 58%

Promoting functions of microRNA-29a/199B in neurological recovery in rats with spinal cord injury through inhibition of the RGMA/STAT3 axis

Yang

Sun

2020

J Orthop Surg Res

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“…MiRNAs are present in all kinds of systems, including the central nervous system, and their dysregulation was related to the multiple neurotraumatic diseases (4). Recently, the role of the miRNAs in SCI development and their value in SCI diagnosis were reported in several papers (5)(6)(7). The microarray analysis revealed that miR-138 expression was signifi cantly enriched in the adult rat spinal cord following SCI (8).…”

Section: Introductionmentioning

confidence: 99%

miRNA-138 regulates MLK3/JNK/MAPK pathway to protect BV-2 cells from H2O2-induced apoptosis

Ren¹,

Chen²,

Fan³

et al. 2018

BLL

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BACKGROUND: miR-138 is one of the down-regulated miRNAs during acute spinal cord injury. Mixed lineage kinase 3 (MLK3), a key factor of jun N-terminal kinase (JNK)/mitogen-activated protein kinase (MAPK) pathway, is the target of miR-138. The aim of this study was to investigate the role of miR-138 in H 2 O 2 -treated BV-2 cells. METHODS: Murine microglia BV-2 cells were treated with H 2 O 2 and tested for cell viability and miR-138 expression. The cells were then transfected with miR-138 agomir or miR-138 antagomir, and treated with 200 μM H 2 O 2 for 24 h. The cellular apoptosis was detected by Aennexin V/PI staining. Expression of miR-138, MLK3, and other factors of JNK/MAPK pathway was detected. RESULTS: After treatment of various concentrations of H 2 O 2 , the cell viabilities were reduced, and miR-138 expression was down-regulated. Compared to the control cells, over-expressing miR-138 in BV-2 cells reduced apoptosis rate from 24.2 % to 11.9 %. Western blot further showed that JNK, p-JNK, c-jun, p-c-jun, p38 MAPK, and p-p38 MAPK were down-regulated. Expression of pro-apoptosis factors iNOS and COX-2 were also downregulated. Transfection of miR-138 antagomir produced the opposite effect of the transfection of miR-138 agomir. CONCLUSION: miR-138 was able to reduce H 2 O 2 -induced apoptosis in BV-2 cells. The protective effect was related to the down-regulation of MLK3 proteins and sequentially inhibiting JNK/MAPK signaling pathway (Fig. 3, Ref. 27). Text in PDF www.elis.sk. KEY WORDS: miR-138, mixed lineage kinase 3, apoptosis, microglia, jun N-terminal kinase.Neurocritical care unit, the second affi liated hospital,

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“…In spinal cord injury (SCI), changes in exosomal miRNAs reflect many of the barriers to CNS regeneration. For example, SCI can differentially regulate exosomal miRNAs that modulate calcium signaling, synaptic function, axon guidance [ 11 – 13 ], axon degeneration, inhibitory molecule expression, and scar tissue formation [ 14 ], suggesting engineered EV combinations may be useful in counteracting or modulating the signaling pathways underlying the default healing response in the CNS. Though EV biology in the visual system is less developed, a number of recent studies indicate EVs, like exosomes and microvesicles, and their cargoes, particularly miRNAs and inflammatory proteins, may be used to detect, monitor, and prognosticate retinal and possibly optic nerve trauma and disease.…”

Section: Evs As Biomarkers In the Visual Systemmentioning

confidence: 99%

Extracellular Vesicles: Biomarkers, Therapeutics, and Vehicles in the Visual System

Merwe

Steketee

2017

Curr Ophthalmol Rep

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PurposeWe discuss recent advances in extracellular vesicle (EV) technology as biomarkers, therapeutics, and drug delivery vehicles in the visual system with an emphasis on the retina.Recent FindingsRetinal cell-type specific EVs can be detected in the blood and in the aqueous humor and EV miRNA cargoes can be used diagnostically to predict retinal disease progression. Studies have now shown EVs can deliver bioactive miRNA and AAV cargoes to the inner retinal cell layers and, in some models, improve retinal ganglion cell (RGC) survival and axon regeneration.SummaryEV molecular profiles and cargoes are attractive biomarkers for retinal and optic nerve disease and trauma and EVs offer a safe and tunable platform for delivering therapies to ocular tissues. However, EVs are heterogeneous by nature with variable lipid membranes, cargoes, and biologic effects, warranting stringent characterization to understand how heterogeneous EV populations modulate positive tissue remodeling.

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Extrinsic and Intrinsic Regulation of Axon Regeneration by MicroRNAs after Spinal Cord Injury

Cited by 30 publications

References 115 publications

Promoting functions of microRNA-29a/199B in neurological recovery in rats with spinal cord injury through inhibition of the RGMA/STAT3 axis

Promoting functions of microRNA-29a/199B in neurological recovery in rats with spinal cord injury through inhibition of the RGMA/STAT3 axis

miRNA-138 regulates MLK3/JNK/MAPK pathway to protect BV-2 cells from H2O2-induced apoptosis

Extracellular Vesicles: Biomarkers, Therapeutics, and Vehicles in the Visual System

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