Repulsive guidance molecule a suppresses angiogenesis after ischemia/reperfusion injury of middle cerebral artery occlusion in rats

Wang, Yu; Zhang, Rongrong; Xing, Xiangfeng; Gui, Jia; Xie, Fei; Zhang, Gang; Qin, Xinyue

doi:10.1016/j.neulet.2017.10.036

Cited by 14 publications

(20 citation statements)

References 33 publications

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“…In addition, there was no difference in RGMA mRNA expression among groups, whereas the protein expression was significantly suppressed by a miR-210-3p mimic, suggesting that this miRNA primarily acts on gene translation and post-translational modification instead of transcription. Our study is the first to report that RGMA is a target of miR-210-3p in EPCs under hypoxia, and is consistent with previous reports (Wang et al, 2018) on the function of RGMA in ECs.…”

Section: Discussionsupporting

confidence: 93%

“…Hypoxia decreases cell viability, migration and invasion while increasing apoptosis. Previous studies demonstrated that miR-210 is upregulated in the serum of patients with acute cerebral infarction and that it might be involved in the pathogenesis of this disease by regulating the proliferation and apoptosis of endothelial cells (Wang et al, 2018). Similar to these results, our study demonstrated that the overexpression of miR-210, and specifically miR-210-3p, is precise and protects EPCs against OGD injury, in addition to enhancing angiogenesis in OGD-treated EPCs.…”

Section: Discussionmentioning

confidence: 99%

“…Zhang et al found that RGMA suppresses the proliferation, tube formation, and migration of ECs by downregulating VEGF and p-FAK (Tyr397) via neogenin and Unc5b in vitro (Zhang et al, 2017). Wang et al reported that RGMA might suppress angiogenesis via VEGF, Ang2, Ang1, and BDNF after cerebral ischemia/reperfusion injury through neogenin, thereby inhibiting neovascularization (Wang et al, 2018). Results of our study found that miR-210-3p overexpression has positive effects on cell proliferation, tube formation, and migration, suggesting that miR-210-3p might function through the negative regulation of RGMA.…”

Section: Discussionmentioning

confidence: 99%

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MicroRNA-210-3p Targets RGMA to Enhance the Angiogenic Functions of Endothelial Progenitor Cells Under Hypoxic Conditions

Liang

et al. 2019

Front. Cell. Neurosci.

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Endothelial progenitor cells (EPCs) are multipotential stem cells considered to have immense clinical value for revascularization. However, the clinical application of EPCs has been hampered by their clinical potency in ischemic anoxic environments. This study aimed to explore the effect of microRNA-210 (miR-210) on EPCs under oxygen-glucose deprivation (OGD) conditions. We generated a model of EPCs cultured under OGD conditions to simulate ischemia and explore the expression of miR-210 in vitro . With longer exposure to hypoxia, we found that miR-210-3p expression was highly upregulated in OGD groups compared to that in controls from 4 to 24 h, but not miR-210-5p. We then transfected a miR-210-3p mimic and inhibitor into EPCs, and after 24 h, we exposed them to OGD conditions for 4 h to simulate ischemia. We detected miR-210 by real-time polymerase chain reaction (RT-PCR) and tested the proliferation, migration, and tube formation of normal EPCs and OGD-treated EPCs by CCK-8, transwell chamber, and Matrigel assays, respectively. The direct targets of miR-210-3p were predicted using miRWalk. Compared to that in normal EPCs, higher miR-210-3p expression was found in OGD-treated EPCs ( p < 0.05). Moreover, upregulation of miR-210-3p was found to promote proliferation, migration, and tube formation in EPCs under normal and OGD conditions ( p < 0.05), whereas down-regulation inhibited these abilities in OGD-treated EPCs ( p < 0.05). Repulsive guidance molecule A (RGMA), a negative regulator of angiogenesis, was predicted to be a target of miR-210-3p. Accordingly, upregulation of miR-210-3p was found to inhibit its expression at the protein level in OGD-treated EPCs, whereas downregulation of miR-210-3p inhibited its expression ( p < 0.05). A dual-luciferase reporter system confirmed that RGMA is a direct target of miR-210-3p. MicroRNA-210-3p overexpression enhances the angiogenic properties of OGD-treated EPCs by inhibiting RGMA.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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MicroRNA-210-3p Targets RGMA to Enhance the Angiogenic Functions of Endothelial Progenitor Cells Under Hypoxic Conditions

Liang

et al. 2019

Front. Cell. Neurosci.

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“…In a previous study, the RGMb expression levels in the brain tissue of rats with MCAO were enhanced and this effect was suggested to be involved in the regeneration and remodeling of axons and synapses after cerebral ischemia injury (20). Furthermore, RGMa suppressed angiogenesis following ischemia and reperfusion injury in a rat MCAO model (21).…”

Section: Introductionmentioning

confidence: 87%

Changes of fractional anisotropy and RGMa in crossed cerebellar diaschisis induced by middle cerebral artery occlusion

et al. 2019

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Crossed cerebellar diaschisis (CCD) is the phenomenon of hypoperfusion and hypometabolism of the contralateral cerebellar hemisphere caused by dysfunction of the associated supratentorial region. The aim of the present study was to analyze the changes in fractional anisotropy (FA) in CCD induced by middle cerebral artery occlusion (MCAO) using magnetic resonance-diffusion tensor imaging (MR-DTI). Furthermore, the role of repulsive guidance molecule a (RGMa) in CCD was assessed by measuring RGMa expression using histochemical analysis. In the present study, the cerebellar hemisphere was serially scanned with T2-weighted, serial diffusion-weighted and diffusion tensor (DT) imaging using a 3.0T GE Signa HDxt Scanner to analyze the changes in FA over 72 h. Subsequently, immunohistochemistry analyses of the corresponding cerebellar hemisphere sections were performed to assess the expression of RGMa. Results indicated that FA of both sides of the cerebellar hemisphere, particularly that of the contralateral cerebellar hemisphere (right side) derived from DTI, was reduced during the 72-h time period following MCAO, and the decrease was maximal and statistically significant at 12 h (P<0.05). Immunohistochemistry analysis revealed a significant increase in the expression of RGMa protein in the affected region of the contralateral cerebellar hemisphere (right side) at 24 h following MCAO injury (P<0.05). Furthermore, the expression of RGMa and FA was negatively correlated in MCAO (P<0.05). The results suggest that MR-DTI is an important assessment to evaluate changes of FA in CCD induced by MCAO. Furthermore, the present results suggest that RGMa, which was negatively correlated with FA in MCAO rats, may serve an important role in CCD.

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“…Removal of Neogenin or Unc5b could significantly reduce the effect of RGMa [ 5 , 34 ]. RGMa can inhibit angiogenesis by down-regulating VEGF and p-FAK (Tyr397) in vitro [ 34 , 35 ]. Recombinant RGMa can also inhibit angiogenesis [ 36 ].…”

Section: Role Of Rgma In Cns Pathologymentioning

confidence: 99%

Repulsive Guidance Molecule-a and Central Nervous System Diseases

Tang

Zeng

et al. 2021

BioMed Research International

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Repulsive guidance molecule-a (RGMa) is a member of glycosylphosphatidylinositol- (GPI-) anchored protein family, which has axon guidance function and is widely involved in the development and pathological processes of the central nervous system (CNS). On the one hand, the binding of RGMa and its receptor Neogenin can regulate axonal guidance, differentiation of neural stem cells into neurons, and the survival of these cells; on the other hand, RGMa can inhibit functional recovery of CNS by inhibiting axonal growth. A number of studies have shown that RGMa may be involved in the pathogenesis of CNS diseases, such as multiple sclerosis, neuromyelitis optica spectrum diseases, cerebral infarction, spinal cord injury, Parkinson’s disease, and epilepsy. Targeting RGMa can enhance the functional recovery of CNS, so it may become a promising target for the treatment of CNS diseases. This article will comprehensively review the research progression of RGMa in various CNS diseases up to date.

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Repulsive guidance molecule a suppresses angiogenesis after ischemia/reperfusion injury of middle cerebral artery occlusion in rats

Cited by 14 publications

References 33 publications

MicroRNA-210-3p Targets RGMA to Enhance the Angiogenic Functions of Endothelial Progenitor Cells Under Hypoxic Conditions

MicroRNA-210-3p Targets RGMA to Enhance the Angiogenic Functions of Endothelial Progenitor Cells Under Hypoxic Conditions

Changes of fractional anisotropy and RGMa in crossed cerebellar diaschisis induced by middle cerebral artery occlusion

Repulsive Guidance Molecule-a and Central Nervous System Diseases

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