Early changes of microRNAs expression in the dorsal root ganglia following rat sciatic nerve transection

Zhou, Songlin; Yu, Bin; Qian, Tianmei; Yao, Dengbing; Wang, Yongjun; Ding, Fei; Gu, Xiaosong

doi:10.1016/j.neulet.2011.02.064

Cited by 48 publications

(34 citation statements)

References 35 publications

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“…It was reported that miRNA expression profiles were significantly altered in the spinal cord injury model of adult rats (Liu et al, 2009a;Strickland et al, 2011). Using microarray analysis, we found that abnormal expression of miRNA in dorsal root ganglia might illustrate the molecular mechanisms of nerve regeneration during the early phase after sciatic nerve transection (Zhou et al, 2011). The role of miRNA in nerve myelination was recently shown by independent studies of Dicer1-deficient oligodendrocytes and SCs (Dugas et al, 2010;Emery, 2010;Pereira et al, 2010;Yun et al, 2010).…”

Section: Introductionmentioning

confidence: 64%

miR-221/222 promote Schwann cell proliferation and migration by targeting LASS2 following sciatic nerve injury

Zhou

Wang

et al. 2012

Journal of Cell Science

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105

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Summary microRNAs (miRNAs) are small non-coding RNAs that regulate gene expression at the post-transcriptional level. Their roles in regulating the responses of Schwann cells (SCs) to injury stimuli remain unexplored. Here we report dynamic alteration of miRNA expression following rat sciatic nerve injury using microarray analysis. We harvested the proximal nerve stumps and identified 77 miRNAs that showed significant changes at four time points after nerve transection. Subsequently, we analyzed the expression pattern of miRNA, selected one significant profile, and then integrated putative miRNA targets with differentially expressed mRNA yielding 274 potential targets. The 274 targets were mainly involved in cell proliferation, cell locomotion and cellular homeostasis that were known to play important roles in modulating cell phenotype. The upregulation of the miR-221 and miR-222 cluster (miR-221/222) was found to correlate with the injury-induced SC phenotypic modulation. Enhanced expression of miR-221/222 could promote SC proliferation and migration in vitro, whereas silencing their expression resulted in a reduced proliferation and migration. Further studies revealed that longevity assurance homologue 2 (LASS2) was a direct target of miR-221/222 in SCs because miR-221/222 bound directly to the 39-untranslated region of LASS2, thus reducing both mRNA and protein levels of LASS2. Silencing of LASS2 recapitulated the effects of miR-221/222 mimics, whereas enforced knockdown of LASS2 reversed the suppressive effects of miR-221/222 inhibitors. Our findings indicate that injury promotes SC proliferation and migration through the regulation of miR-221/222 by targeting LASS2, and provide new insights into the role of miRNAs in nerve regeneration.

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Section: Introductionmentioning

confidence: 64%

miR-221/222 promote Schwann cell proliferation and migration by targeting LASS2 following sciatic nerve injury

Zhou

Wang

et al. 2012

Journal of Cell Science

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105

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“…(Table S2). The data summarized all possible expression trends and statistical judgments, in accordance with P <0.05/N as the standard [22,23,25] .…”

Section: Discussionmentioning

confidence: 99%

“…It offers an updated, dynamic and controlled vocabulary for strictly defining concepts in describing the properties of genes and their related proteins. GO has three ontologies: biological process, cellular component, and molecular function [22,23,25] .…”

Section: Gene Expression Profiling and Regulationmentioning

confidence: 99%

Expression changes and bioinformatic analysis of Wallerian degeneration after sciatic nerve injury in rat

Yao

Shen

et al. 2013

Neurosci. Bull.

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Wallerian degeneration (WD) remains an important research topic. Many genes are differentially expressed during the process of WD, but the precise mechanisms responsible for these differentiations are not completely understood. In this study, we used microarrays to analyze the expression changes of the distal nerve stump at 0, 1, 4, 7, 14, 21 and 28 days after sciatic nerve injury in rats. The data revealed 6 076 differentially-expressed genes, with 23 types of expression, specifically enriched in genes associated with nerve development and axonogenesis, cytokine biosynthesis, cell differentiation, cytokine/chemokine production, neuron differentiation, cytokinesis, phosphorylation and axon regeneration. Kyoto Encyclopedia of Genes and Genomes pathway analysis gave findings related mainly to the MAPK signaling pathway, the Jak-STAT signaling pathway, the cell cycle, cytokine-cytokine receptor interaction, the p53 signaling pathway and the Wnt signaling pathway. Some key factors were NGF, MAG, CNTF, CTNNA2, p53, JAK2, PLCB1, STAT3, BDNF, PRKC, collagen II, FGF, THBS4, TNC and c-Src, which were further validated by real-time quantitative PCR, Western blot, and immunohistochemistry. Our findings contribute to a better understanding of the functional analysis of differentially-expressed genes in WD and may shed light on the molecular mechanisms of nerve degeneration and regeneration.

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“…In comparison to the study of miRNAs in many other biological events, the importance of miRNAs in peripheral nerve injury and regeneration has not been fully investigated. Our previous study using microarray and deep sequencing showed that abnormal expression of miRNAs in dorsal root ganglia was involved in nerve regeneration after transection to rat sciatic nerves Zhou et al, 2011). The role of miRNAs in nerve myelination has been investigated by two independent studies on Dicer1-deficient Schwann cells (Pereira et al, 2010;Yun et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

miR-9 inhibits Schwann cell migration by targeting CTHRC1 following sciatic nerve injury

Zhou

Gao

et al. 2014

Journal of Cell Science

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The regulative effects of microRNAs (miRNAs) on responses of Schwann cells to a nerve injury stimulus are not yet clear. In this study, we noted that the expression of eight miRNAs was downregulated at different time points following rat sciatic nerve transection, and found that 368 potential targets of these eight miRNAs were mainly involved in phenotypic modulation of Schwann cells. Of these miRNAs, miR-9 was identified as an important functional regulator of Schwann cell migration that was a crucial regenerative response of Schwann cells to nerve injury. In vitro, upregulated expression of miR-9 inhibited Schwann cell migration, whereas silencing of miR-9 promoted Schwann cell migration. Intriguingly, miR-9 exerted this regulative function by directly targeting collagen triple helix repeat containing protein 1 (CTHRC1), which in turn inactivated downstream Rac1 GTPase. Rac1 inhibitor reduced the promotive effects of anti-miR-9 on Schwann cell migration. In vivo, high expression of miR-9 reduced Schwann cell migration within a regenerative nerve microenvironment. Collectively, our results confirmed the role of miR-9 in regulating Schwann cell migration after nerve injury, thus offering a new approach to peripheral nerve repair.

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Early changes of microRNAs expression in the dorsal root ganglia following rat sciatic nerve transection

Cited by 48 publications

References 35 publications

miR-221/222 promote Schwann cell proliferation and migration by targeting LASS2 following sciatic nerve injury

miR-221/222 promote Schwann cell proliferation and migration by targeting LASS2 following sciatic nerve injury

Expression changes and bioinformatic analysis of Wallerian degeneration after sciatic nerve injury in rat

miR-9 inhibits Schwann cell migration by targeting CTHRC1 following sciatic nerve injury

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