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Wnts are expressed in the spinal cord of adult mice and are differentially induced after injury.

ABSTRACT: The Wnt family of proteins plays key roles during central nervous system development and has been involved in several neuropathologies during adulthood, including spinal cord injury (SCI). However, Wnts expression knowledge is relatively limited during adult stages. Here, we sought to define the Wnt family expression pattern after SCI in adult mice by using quantitative polymerase chain reaction (qPCR) and immunohistochemistry (IHC). Under physiological conditions, the messenger RNAs (mRNAs) of most Wnt ligands, inhibitors, receptors, and coreceptors are constitutively expressed in healthy adult mice. After dorsal hemisection, we found significant time-dependent variations, with a prominent up-regulation of Wnt inhibitory factor 1 (Wif1). IHC against Frizzled (Fz) 1 and Fz4, as representatives of late and acute up-regulated receptors, showed a differential expression in the uninjured spinal cord of Fz1 by neurons and oligodendrocytes and Fz4 by astrocytes. After injury, both receptors were maintained in the same type of cells. Finally, by using BATgal reporter mice, our results revealed active ?-catenin signaling in neurons of the dorsal horn and cells of the central canal of uninjured spinal cords, besides a lack of additional SCI-induced activation. In conclusion, we demonstrate Wnt expression in the adult spinal cord of mice that is modulated by SCI, which differs from that previously described in rats. Further, Fz receptors are differentially expressed by neurons and glial cells, suggestive for cell-specific patterns and thus diverse physiological roles. Further studies will help toward in-depth characterization of the role of all Wnt factors and receptors described and eventually allow for the design of novel therapies.

SUBMITTER: Gonzalez-Fernandez C

PROVIDER: S-EPMC3949505 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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Wnts are expressed in the spinal cord of adult mice and are differentially induced after injury.

González-Fernández Carlos C Fernández-Martos Carmen María CM Shields Shannon D SD Arenas Ernest E Javier Rodríguez Francisco F

Journal of neurotrauma 20140301 6

The Wnt family of proteins plays key roles during central nervous system development and has been involved in several neuropathologies during adulthood, including spinal cord injury (SCI). However, Wnts expression knowledge is relatively limited during adult stages. Here, we sought to define the Wnt family expression pattern after SCI in adult mice by using quantitative polymerase chain reaction (qPCR) and immunohistochemistry (IHC). Under physiological conditions, the messenger RNAs (mRNAs) of ...[more]

PMID: 24367909

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Project description:In the search for a therapeutic schedule for spinal cord injury, it is necessary to understand key genes and their corresponding regulatory networks involved in the spinal cord injury process. However, ad hoc selection and analysis of one or two genes cannot fully reveal the complex molecular biological mechanisms of spinal cord injury. The emergence of second-generation sequencing technology (RNA sequencing) has provided a better method. In this study, RNA sequencing technology was used to analyze differentially expressed genes at different time points after spinal cord injury in rat models established by contusion of the eighth thoracic segment. The numbers of genes that changed significantly were 944, 1362 and 1421 at 1, 4 and 7 days after spinal cord injury respectively. After gene ontology analysis and temporal expression analysis of the differentially expressed genes, C5ar1, Socs3 and CCL6 genes were then selected and identified by real-time polymerase chain reaction and western blot assay. The mRNA expression trends of C5ar1, Socs3 and CCL6 genes were consistent with the RNA sequencing results. Further verification and analysis of C5ar1 indicate that the level of protein expression of C5ar1 was consistent with its nucleic acid level after spinal cord injury. C5ar1 was mainly expressed in neurons and astrocytes. Finally, the gene Itgb2, which may be related to C5ar1, was found by Chilibot database and literature search. Immunofluorescence histochemical results showed that the expression of Itgb2 was highly consistent with that of C5ar1. Itgb2 was expressed in astrocytes. RNA sequencing technology can screen differentially expressed genes at different time points after spinal cord injury. Through analysis and verification, genes strongly associated with spinal cord injury can be screened. This can provide experimental data for further determining the molecular mechanism of spinal cord injury, and also provide possible targets for the treatment of spinal cord injury. This study was approved ethically by the Laboratory Animal Ethics Committee of Jiangsu Province, China (approval No. 2018-0306-001) on March 6, 2018.

Project description:Complex pathological changes occur during the development of spinal cord injury (SCI), and determining the underlying molecular events that occur during SCI is necessary for the development of promising molecular targets and therapeutic strategies. This study was designed to explore differentially expressed genes (DEGs) associated with the acute and chronic stages of SCI using bioinformatics analysis. Gene expression profiles (GSE45006, GSE93249, and GSE45550) were downloaded from the Gene Expression Omnibus database. SCI-associated DEGs from rat samples were identified, and Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed. In addition, a protein-protein interaction network was constructed. Approximately 66 DEGs were identified in GSE45550 between 3-14 days after SCI, whereas 2418 DEGs were identified in GSE45006 1-56 days after SCI. Moreover, 1263, 195, and 75 overlapping DEGs were identified between these two expression profiles, 3, 7/8, and 14 days after SCI, respectively. Additionally, 16 overlapping DEGs were obtained in GSE45006 1-14 days after SCI, including Pank1, Hn1, Tmem150c, Rgd1309676, Lpl, Mdh1, Nnt, Loc100912219, Large1, Baiap2, Slc24a2, Fundc2, Mrps14, Slc16a7, Obfc1, and Alpk3. Importantly, 3882 overlapping DEGs were identified in GSE93249 1-6 months after SCI, including 3316 protein-coding genes and 567 long non-coding RNA genes. A comparative analysis between GSE93249 and GSE45006 resulted in the enrichment of 1135 overlapping DEGs. The significant functions of these 1135 genes were correlated with the response to the immune effector process, the innate immune response, and cytokine production. Moreover, the biological processes and KEGG pathways of the overlapping DEGs were significantly enriched in immune system-related pathways, osteoclast differentiation, the nuclear factor-κB signaling pathway, and the chemokine signaling pathway. Finally, an analysis of the overlapping DEGs associated with both acute and chronic SCI, assessed using the expression profiles GSE93249 and GSE45006, identified four overlapping DEGs: Slc16a7, Alpk3, Lpl and Nnt. These findings may be useful for revealing the biological processes associated with SCI and the development of targeted intervention strategies.

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Project description:Spinal cord injury (SCI) remains one kind of devastating neurological damage, and specific molecular mechanisms involved need to be understood deeply. Currently, circular RNAs (circRNAs), as a newly discovered type of non-coding RNAs (ncRNAs), have been under active investigation. Through functional interactions with disease-associated microRNAs (miRNAs), exosome-derived circRNAs have been extensively implicated in various organ pathogenesis. Nevertheless, the functional involvement of circulating circRNAs in SCI onset, progression as well as repair remains poorly explored until now. Of note, there still lacks clinical and experimental evidence in this regard. To obtain some relevant knowledge in this field, this study was originally designed to have a general overview of differentially expressed circRNAs derived from circulating exosomes in SCI rats in comparison with the control rats. It turned out that 709 types of downregulated circRNAs and 346 kinds of upregulated circRNAs were preliminarily screened out. Functional enrichment analyses including kyoto encyclopedia of genes and genomes (KEGG) pathway and gene ontology (GO) were performed to evaluate the possible biological functions of upregulated as well as downregulated circRNAs involved in SCI. Furthermore, five types of upregulated circulating circRNAs including chr4:208359914-208362182+, chr15:20088296-20092102+, chr1:175098934- 175134845-, chr1:175099657- 175128203-, and chr1:175104454- 175134845-, and plus five kinds of downregulated circulating circRNAs including chr11:74154652- 74159524-, chr12:45412398- 45412635-, chr7:137630261- 137648924-, chr6:6280974-6281188+, and chr4:225251864-225254087+, were verified through reverse transcription-polymerase chain reaction (RT-PCR). At last, taking these differentially expressed circRNAs in the center, the circRNA-miRNA-mRNA gene interaction network was constructed to predict the possible functionalities of circRNAs in SCI through anticipating specific interactive miRNAs, giving new insights into how circRNAs contribute to this pathological process. Taken together, these findings suggest the possible involvement and functional significance of circRNAs in SCI.

Dataset Information

Wnts are expressed in the spinal cord of adult mice and are differentially induced after injury.

Publications

Wnts are expressed in the spinal cord of adult mice and are differentially induced after injury.

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