miR-20a Promotes the Axon Regeneration of DRG Neurons by Targeting Nr4a3

Zhao, Lili; Gong, Leilei; Li, Ping; Qin, Jing; Xu, Lingchi; Wei, Qi-Yao; Xie, Huimin; Mao, Susu; Yu, Bin; Gu, Xiaosong; Zhou, Songlin

doi:10.1007/s12264-021-00647-2

Cited by 9 publications

(7 citation statements)

References 15 publications

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“…In previous studies, a large number of transcriptomic and proteomic analyses were employed in DRG or sciatic nerve after nerve injury, and a series of transcriptional factors, epigenetic proteins that induce or enhance axon regeneration were acquired 4–8 . Additionally, our studies have revealed that noncoding RNAs also play key roles in nerve repair after injury 9–12 13–15 .…”

Section: Introductionmentioning

confidence: 81%

“…[4][5][6][7][8] Additionally, our studies have revealed that noncoding RNAs also play key roles in nerve repair after injury. [9][10][11][12] Very recently, the single-cell RNA sequencing (scRNA-seq) was used to describe gene expression profiles in injured peripheral nervous tissue at cellular resolution. [13][14][15] Axonal regeneration of neurons is a process in an urgent need of energy and matter, which requires a large amount of lipid supply, protein and nucleic acid synthesis.…”

Section: Introductionmentioning

confidence: 99%

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The metabolomic profiling identifies N, N‐dimethylglycine as a facilitator of dorsal root ganglia neuron axon regeneration after injury

et al. 2022

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Identifying novel molecules involved in axon regeneration of neurons in the peripheral nervous system (PNS) will be of benefit in obtaining a therapeutic strategy for repairing axon damage both in the PNS and the central nervous system (CNS). Metabolism and axon regeneration are tightly connected. However, the overall metabolic processes and the landscape of the metabolites in axon regeneration of PNS neurons are uncovered. Here, we used an ultra high performance liquid tandem chromatography quadrupole time of flight mass spectrometry (UHPLC‐QTOFMS)‐based untargeted metabolomics to analyze dorsal root ganglia (DRG) metabolic characteristics at different time points post sciatic nerve injury and acquired hundreds of differentially changed metabolites. In addition, the results reveal that several metabolic pathways were significantly altered, such as ‘Histidine metabolism’, ‘Glycine serine and threonine metabolism’, ‘Arginine and proline metabolism’, ‘taurine and hypotaurine metabolism’ and so on. Given metabolite could alter a cell's or an organism's phenotype, further investigation demonstrated that N, N‐dimethylglycine (DMG) has a promoting effect on the regenerative ability post injury. Overall, our data may serve as a resource useful for further understanding how metabolites contribute to axon regeneration in DRG during sciatic nerve regeneration and suggest DMG may be a candidate drug to repair nerve injury.

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Section: Introductionmentioning

confidence: 81%

Section: Introductionmentioning

confidence: 99%

The metabolomic profiling identifies N, N‐dimethylglycine as a facilitator of dorsal root ganglia neuron axon regeneration after injury

et al. 2022

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“…In clinical studies, miR-20a was upregulated in serum samples of multiple system atrophy and AD patients ( Cheng et al , 2015 ; Kume et al , 2018 ), whereas it was downregulated in blood samples of MS patients ( Cox et al , 2010 ), implying diverse miRNA regulation across different types of neurodegenerative diseases. Notably, miR-20a inhibition in rat dorsal root ganglia (DRG) was shown to impair neurite outgrowth, emphasizing the important role miR-20a may play in neurodegeneration ( Zhao et al , 2021 ).…”

Section: Resultsmentioning

confidence: 99%

“…miR-20a upregulated during the axon regeneration of DRG neurons, supporting the neurite outgrowth ( Zhao et al , 2021 )…”

Section: Resultsmentioning

confidence: 99%

“…We specifically focused on secreted biomarkers in vitro, since secreted factors would be most likely to translate to detection of miRNAs in fluids (serum, CSF, and urine) of animals or humans. Additionally, these miRNAs were previously shown to be altered in a variety of nonclinical systems, such as human neuroblastoma and neural progenitor cells, and nonclinical species including mice and rats under neurotoxic conditions ( Aranha et al , 2010 ; Beveridge et al , 2009 ; Feng et al , 2020 ; Jeyaseelan et al , 2008 ; Jian et al , 2019 ; Jin et al , 2021 ; Liu et al , 2015 ; Shen et al , 2020 ; Song et al , 2019 ; Wang and Jia, 2021 ; Wang et al , 2016 , 2020 ; Wei et al , 2015 ; Yang et al , 2021 ; Zhang et al , 2014 ; Zhao et al , 2017 , 2021 ; Zhong et al , 2020 ). This suggests a strong translation of effect across species and increases our confidence that these notable miRNAs may be predictive biomarkers of chemical-induced neurodegeneration in nonclinical safety studies and in humans.…”

Section: Discussionmentioning

confidence: 99%

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Profiling Secreted miRNA Biomarkers of Chemical-Induced Neurodegeneration in Human iPSC-Derived Neurons

You

Cohen

Pustovalova

et al. 2022

Toxicological Sciences

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Elucidation of predictive fluidic biochemical markers to detect and monitor chemical-induced neurodegeneration has been a major challenge due to a lack of understanding of molecular mechanisms driving altered neuronal morphology and function, as well as poor sensitivity in methods to quantify low-level biomarkers in bodily fluids. Here, we evaluated five neurotoxicants (acetaminophen [negative control], bisindolylmaleimide-1, colchicine, doxorubicin, paclitaxel, and rotenone) in human iPSC-derived neurons to profile secreted miRNAs at early and late stages of decline in neuronal cell morphology and viability. Based on evaluation of these morphological (neurite outgrowth parameters) and viability (ATP) changes, two concentrations of each chemical were selected for analysis in a human 754 miRNA panel: a low concentration with no/minimal effect on cell viability but a significant decrease in neurite outgrowth, and a high concentration with a significant decrease in both endpoints. A total of 39 miRNAs demonstrated significant changes (fold-change ≥1.5 or ≤ 0.67, p-value < 0.01) with at least one exposure. Further analyses of targets modulated by these miRNAs revealed 38 key mRNA targets with roles in neurological dysfunctions, and identified TGF-β signaling as a commonly enriched pathway. Of the 39 miRNAs, five miRNAs, three down-regulated (miR-20a, miR-30b, and miR-30d) and two up-regulated (miR-1243 and miR-1305), correlated well with morphological changes induced by multiple neurotoxicants and were notable based on their relationship to various neurodegenerative conditions and/or key pathways, such as TGF-β signaling. These data sets reveal miRNA candidates that warrant further evaluation as potential safety biomarkers of chemical-induced neurodegeneration.

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Gas5 inhibition promotes the axon regeneration in the adult mammalian nervous system

Han

Chen

et al. 2022

Experimental Neurology

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miR-20a Promotes the Axon Regeneration of DRG Neurons by Targeting Nr4a3

Cited by 9 publications

References 15 publications

The metabolomic profiling identifies N, N‐dimethylglycine as a facilitator of dorsal root ganglia neuron axon regeneration after injury

The metabolomic profiling identifies N, N‐dimethylglycine as a facilitator of dorsal root ganglia neuron axon regeneration after injury

Profiling Secreted miRNA Biomarkers of Chemical-Induced Neurodegeneration in Human iPSC-Derived Neurons

Gas5 inhibition promotes the axon regeneration in the adult mammalian nervous system

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