Repulsive guidance molecule A (RGMa)

Key, Brian; Lah, Grace J.

doi:10.4161/cam.20167

Cited by 17 publications

(15 citation statements)

References 23 publications

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“…Both DMRs, containing different sets of CpG sites, were located at a CpG island, one situated at a promoter, the other at an intron, and showed hypomethylation for both associations, which could be indicative of a transcriptional upregulation. In addition, we identified DMRs annotated to RGMA , which has an important role in neurological development and operates through axon guidance and programmed apoptosis in the developing embryonic neural tube (Matsunaga et al, 2004; Key and Lah, 2012). RGMA is associated with the selective degeneration of dopaminergic neurons in the substantia nigra in a Parkinson’s disease model in mice (Korecka et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

The Cord Blood Insulin and Mitochondrial DNA Content Related Methylome

et al. 2019

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Mitochondrial dysfunction seems to play a key role in the etiology of insulin resistance. At birth, a link has already been established between mitochondrial DNA (mtDNA) content and insulin levels in cord blood. In this study, we explore shared epigenetic mechanisms of the association between mtDNA content and insulin levels, supporting the developmental origins of this link. First, the association between cord blood insulin and mtDNA content in 882 newborns of the ENVIR ON AGE birth cohort was assessed. Cord blood mtDNA content was established via qPCR, while cord blood levels of insulin were determined using electrochemiluminescence immunoassays. Then the cord blood DNA methylome and transcriptome were determined in 179 newborns, using the human 450K methylation Illumina and Agilent Whole Human Genome 8 × 60 K microarrays, respectively. Subsequently, we performed an epigenome-wide association study (EWAS) adjusted for different maternal and neonatal variables. Afterward, we focused on the 20 strongest associations based on p -values to assign transcriptomic correlates and allocate corresponding pathways employing the R packages ReactomePA and RDAVIDWebService. On the regional level, we examined differential methylation using the DMRcate and Bumphunter packages in R. Cord blood mtDNA content and insulin were significantly correlated ( r = 0.074, p = 0.028), still showing a trend after additional adjustment for maternal and neonatal variables ( p = 0.062). We found an overlap of 33 pathways which were in common between the association with cord blood mtDNA content and insulin levels, including pathways of neurodevelopment, histone modification, cytochromes P450 (CYP)-metabolism, and biological aging. We further identified a DMR annotated to Repulsive Guidance Molecule BMP Co-Receptor A ( RGMA ) linked to cord blood insulin as well as mtDNA content. Metabolic variation in early life represented by neonatal insulin levels and mtDNA content might reflect or accommodate alterations in neurodevelopment, histone modification, CYP-metabolism, and aging, indicating etiological origins in epigenetic programming. Variation in metabolic hormones at birth, reflected by molecular changes, might via these alterations predispose children to metabolic diseases later in life. The results of this study may provide important markers for following targeted studies.

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Section: Discussionmentioning

confidence: 99%

The Cord Blood Insulin and Mitochondrial DNA Content Related Methylome

et al. 2019

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“…One such guidance protein, repulsive guidance molecule-A (RGM-A), a glycosylphosphatidylinositol (GPI)-linked membrane glycoprotein, mediates chemorepulsive signals to steer axonal growth cones to their targets in the brain 2,3 . Studies have shown notable guidance roles for RGM-A and its receptor neogenin during embryonic development and morphogenetic processes including cell adhesion, cell migration, cell polarity and cell differentiation 4,5 . Recent evidence identified RGM-A in peripheral tissues, where it was shown to play crucial roles in the onset of an acute inflammatory response and in the pathology of autoimmune encephalomyelitis 6–8 .…”

Section: Introductionmentioning

confidence: 99%

Sympathetic nervous system controls resolution of inflammation via regulation of repulsive guidance molecule A

Körner

Schlegel

Kaussen³

et al. 2019

Nat Commun

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The bidirectional communication between the immune and nervous system is important in regulating immune responses. Here we show that the adrenergic nerves of sympathetic nervous system orchestrate inflammation resolution and regenerative programs by modulating repulsive guidance molecule A (RGM-A). In murine peritonitis, adrenergic nerves and RGM-A show bidirectional activation by stimulating the mutual expression and exhibit a higher potency for the cessation of neutrophil infiltration; this reduction is accompanied by increased pro-resolving monocyte or macrophage recruitment, polymorphonucleocyte clearance and specialized pro-resolving lipid mediators production at sites of injury. Chemical sympathectomy results in hyperinflammation and ineffective resolution in mice, while RGM-A treatments reverse these phenotypes. Signalling network analyses imply that RGM-A and β2AR agonist regulate monocyte activation by suppressing NF-κB activity but activating RICTOR and PI3K/AKT signalling. Our results thus illustrate the function of sympathetic nervous system and RGM-A in regulating resolution and tissue repair in a murine acute peritonitis model.

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“…The repulsive guidance molecule a(RGMa) has been demonstrated to impede neurite outgrowth in postnatal cerebellar neurons (16,17). In rats, the induction of RGMa expression following spinal cord injury at the site of the lesion has been observed (18). Neutralization of RGMa with local administration of an antibody was identified to significantly facilitate axon regeneration following spinal cord injury (15,19).…”

Section: Introductionmentioning

confidence: 99%

“…Neutralization of RGMa with local administration of an antibody was identified to significantly facilitate axon regeneration following spinal cord injury (15,19). In addition, RGMa has been indicated to participate in the development of scar tissue following injury and in the myelination of fiber tracts (18). Furthermore, RGMa has been indicated to be one of the most potent inhibitors of axonal growth (17).…”

Section: Introductionmentioning

confidence: 99%

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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Repulsive guidance molecule A (RGMa)

Cited by 17 publications

References 23 publications

The Cord Blood Insulin and Mitochondrial DNA Content Related Methylome

The Cord Blood Insulin and Mitochondrial DNA Content Related Methylome

Sympathetic nervous system controls resolution of inflammation via regulation of repulsive guidance molecule A

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

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