SGK1 in Schwann cells is a potential molecular switch involved in axonal and glial regeneration during peripheral nerve injury

Okura, Atsuhiko; Inoue, Kōichi; Sakuma, Eisuke; Takase, Hiroshi; Ueki, Takatoshi; Mase, Mitsuhito

doi:10.1016/j.bbrc.2022.03.123

Cited by 8 publications

(4 citation statements)

References 42 publications

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“…Interestingly, MR and GR target gene Sgk1 total knockout in mouse resulted in a decreased g-ratio of the same magnitude than in SCMRKO animals, and suggested that SGK1 regulates myelination by phosphorylating NDRG1 (Heller et al 2014). Moreover, it has been recently proposed that SGK may be a molecular switch for glial regeneration after injury in the PNS (Okura et al 2022). This further highlight a potential involvement of glucocorticoid signaling in peripheral myelination.…”

Section: Discussionmentioning

confidence: 84%

Mineralocorticoid receptor knockout in Schwann cells alters myelin sheath thickness

González-Mayoral,

Eid,

Derounian

et al. 2023

Journal of Endocrinology

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Myelination allows fast and synchronized nerve influxes and is provided by Schwann cells in the peripheral nervous system. Glucocorticoid hormones are major regulators of stress, metabolism and immunity affecting all tissues. They act by binding to two receptors, the low affinity glucocorticoid receptor (GR) and the high affinity mineralocorticoid receptor (MR). Little is known on the effect of glucocorticoid hormones on the PNS and this study focuses on deciphering the role of MR in peripheral myelination. In this work, the presence of a functional MR in Schwann cells is demonstrated and the expression of MR protein in mouse sciatic nerve SC is evidenced. Besides, knockout of MR in SC (SCMRKO using Cre-lox system with DesertHedgeHog (Dhh) Cre promoter) was undertaken in mice. SCMRKO was not associated with alterations of performance in motor behavioral tests on 2- to 6-month old male mice compared to their controls. No obvious modifications of myelin gene expression or MR signaling gene expression were observed in the SCMRKO sciatic nerves. Nevertheless, Gr transcript and GR protein amounts were significantly increased in SCMRKO nerves compared to controls, suggesting a possible compensatory effect. Besides, an increase in myelin sheath thickness was noted for axons with perimeters larger than 15 µm in SCMRKO illustrated by a significant 4.5 % reduction in g-ratio (axon perimeter/myelin sheath perimeter). Thus, we defined MR as a new player in peripheral system myelination and in SC homeostasis.

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Section: Discussionmentioning

confidence: 84%

Mineralocorticoid receptor knockout in Schwann cells alters myelin sheath thickness

González-Mayoral,

Eid,

Derounian

et al. 2023

Journal of Endocrinology

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“…Sgk1 is a protein kinase that plays a role in various cellular processes, including ion transport, cell survival, proliferation, and apoptosis. 43 , 44 Dusp1 was correlated with 3 LncRNAs, and it is considered a stress‐responsive gene and is involved in the cellular response to stress. 45 The mRNAs Mt2A, Zbtb16 and Apold1 were correlated with 2 LncRNAs, previous study has shown that Mt2A is involved in the anti‐inflammatory response, 46 Zbtb16 is involved in energy metabolism, 47 and Apold1 is involved in acute stress response.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, in this co‐expression network between DE lncRNAs and mRNAs, we found that Sgk1 was correlated with 4 LncRNAs. Sgk1 is a protein kinase that plays a role in various cellular processes, including ion transport, cell survival, proliferation, and apoptosis 43,44 . Dusp1 was correlated with 3 LncRNAs, and it is considered a stress‐responsive gene and is involved in the cellular response to stress 45 .…”

Section: Discussionmentioning

confidence: 99%

Molecular profile of vestibular compensation in the medial vestibular nucleus after unilateral labyrinthectomy

Wang,

Liu,

Tian

et al. 2024

J Cellular Molecular Medi

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Long non‐coding RNAs (lncRNAs) have emerged as crucial regulators in the central nervous system, yet their role in vestibular compensation remains elusive. To address this knowledge gap, we employed unilateral labyrinthectomy (UL) in rats to establish animal models of peripheral vestibular dysfunction. Utilizing ribonucleic acid sequencing (RNA‐seq), we comprehensively analysed the expression profiles of genes dysregulated in the medial vestibular nucleus (MVN) of these rats at distinct time points: 4 h, 4 days, and 14 days post‐UL. Through trans‐target prediction analysis integrating differentially co‐expressed messenger RNAs (mRNAs) and lncRNAs, we constructed lncRNA‐mRNA regulatory networks. Validation of selected mRNAs and lncRNAs was performed using RT‐qPCR. Our RNA‐seq analysis revealed significant aberrant expression of 3054 lncRNAs and 1135 mRNAs compared to control samples. By applying weighted gene co‐expression network analysis (WGCNA), we identified 11 co‐expressed modules encompassing all genes. Notably, within the MEmagenta module, we observed an initial upregulation of differentially expressed genes (DEGs) at 4 h, followed by downregulation at 4‐ and 14‐days post‐UL. Our findings indicated that 3068 lncRNAs positively regulated 1259 DEGs, while 1482 lncRNAs negatively regulated 433 DEGs in the MVN. The RT‐qPCR results corroborated the RNA‐seq data, validating our findings. This study offers novel insights into the lncRNA‐mRNA expression landscape during vestibular compensation, paving the way for further exploration of lncRNA functions in this context.

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“…For illustration, we used FSM to search for fully connected networks ("cliques") with at least four genes and found a single module -Sgk1, Ttyh2, Ndrg1 and Ermn (Figure 6g) -that is colocalized in 72 cells, far greater than the support of the next most frequent four-gene clique (12 cells) (Figures 6i-k). The six gene pairs comprising this module are d-colocalized individually, is specific to mature oligodendrocytes and the module is significantly associated (p-value 8.3e-3) with myelin sheath [56][57][58][59] (Figure 6h). We speculate that their co-localization in specific partitions inside cell reflects coordinated transport and translation in mature oligodendrocytes.…”

Section: Instant Reveals Modules Of Genes Colocalizing With Each Othermentioning

confidence: 99%

Intracellular Spatial Transcriptomic Analysis Toolkit (InSTAnT)

Kumar

Schrader

Boroojeny

et al. 2023

Preprint

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Imaging-based spatial transcriptomics technologies such as MERFISH offer snapshots of cellular processes in unprecedented detail, but new analytic tools are needed to realize their full potential. We present InSTAnT, a computational toolkit for extracting molecular relationships from spatial transcriptomics data at the intra-cellular resolution. InSTAnT detects gene pairs and modules with interesting patterns of mutual co-localization within and across cells, using specialized statistical tests and graph mining. We showcase the toolkit on datasets profiling a human cancer cell line and hypothalamic preoptic region of mouse brain. We performed rigorous statistical assessment of discovered co-localization patterns, found supporting evidence from databases and RNA interactions, and identified subcellular domains associated with RNA-colocalization. We identified several novel cell type-specific gene co-localizations in the brain. Intra-cellular spatial patterns discovered by InSTAnT mirror diverse molecular relationships, including RNA interactions and shared sub-cellular localization or function, providing a rich compendium of testable hypotheses regarding molecular functions.

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SGK1 in Schwann cells is a potential molecular switch involved in axonal and glial regeneration during peripheral nerve injury

Cited by 8 publications

References 42 publications

Mineralocorticoid receptor knockout in Schwann cells alters myelin sheath thickness

Mineralocorticoid receptor knockout in Schwann cells alters myelin sheath thickness

Molecular profile of vestibular compensation in the medial vestibular nucleus after unilateral labyrinthectomy

Intracellular Spatial Transcriptomic Analysis Toolkit (InSTAnT)

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