Downregulation of LncRNA Gas5 inhibits apoptosis and inflammation after spinal cord ischemia-reperfusion in rats

Zhang, Zaili; Li, Xiaoqian; Chen, Fengshou; Li, Zhe; Wang, Dan; Ren, Xiaoyan; Ma, Hong

doi:10.1016/j.brainresbull.2020.12.005

Cited by 23 publications

(14 citation statements)

References 36 publications

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“…In bactericidal and anti-in ammatory roles, MMP7-de cient mice are strongly protected against an otherwise lethal dose of LPS [27]. In our previous study [17], we suggested silencing lncRNA Gas5 protected against SCII in a rat-model by regulating MMP-7, but the speci c mechanism of MMP-7 remained unclear. In this study, MMP-7 expression was greatly upregulated along with the reduction of Tarlov scores after SCII, suggesting a probable relation between MMP-7 and dyskinesia.…”

Section: Discussionmentioning

confidence: 95%

“…In neurological diseases, MMP-7 is greatly increased in rat sciatic nerve segments after nerve injury [14]; and MMP-7 is on the regulation of Schwann cell phenotype and the regeneration of injured peripheral nerves [15]; and MMP-7 removes remyelinationimpairing bronectin aggregates in multiple sclerosis lesions [16]. Additionally, it has been con rmed in our previous study that MMP-7 was involved in SCII [17], but the mechanism has not been fully understood. In this study, we explore the speci c role of MMP-7 in the pathogenesis of SCII to provide a theoretical basis for nding effective therapies.…”

Section: Introductionmentioning

confidence: 99%

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The Roles of Matrix Metalloproteinase 7 in Spinal Cord Ischemia- Reperfusion Injury in Rats

Fang¹,

Chen²,

Wang³

et al. 2021

Preprint

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Background: Neuronal survival after spinal cord ischemia-reperfusion injury (SCII) is a major factor affecting the motor function. Recently, matrix metalloproteinase-7 (MMP-7) plays an important role in a variety of diseases, but the specific role of MMP-7 in SCII remains unclear. This paper aims to further investigate the role of MMP7 in SCII.Methods: We built the SCII model by clipping the aortic arch for 14 minutes. The RNA and protein expression of MMP-7 was detected by Western blot and real-time polymerase chain reaction (PCR) during the groups. The co-localization of major cell types and MMP-7 in the spinal cords was detected by Immunofluorescence staining. To further study the specific mechanism, rats were intrathecally pretreated with si-MMP7 or negative control (NC) siRNA 3 days before clipping the aortic arch for 14 minutes. The Tarlov criteria and Haematoxylin and eosin staining were used to detect neurological function and histological assessment. Western blot, PCR and Immunofluorescence staining were used to evaluate the effect of silencing MMP-7.Results: The expression of MMP-7 RNA and protein increased both at 12 h and 24 h after SCII. At 24 h after SCII, the expression of MMP-7 RNA reached its maximum amount. Compared with the sham group, MMP-7 fluorescent expression in the SCII group greatly enhanced, and MMP-7 fluorescence was mainly co-expressed with neuronal nuclei (NeuN) fluorescence. The Tarlov scores and number of intact neurons were increased by pre-treatment with si-MMP7. Pre-treatment with si-MMP7 could also decrease the expression of MMP-7, Interleukin-1β (IL-1β) and cleaved caspase-3 and reduce the MMP-7 expression in neurons. Conclusions: Silencing MMP-7 protected the rats against SCII by inhibiting the neuroapoptosis and inflammation. Silencing MMP-7 could be a hopeful therapeutic treatment after SCII.

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Section: Discussionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

The Roles of Matrix Metalloproteinase 7 in Spinal Cord Ischemia- Reperfusion Injury in Rats

Fang¹,

Chen²,

Wang³

et al. 2021

Preprint

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“…Subsequently, NF-κB translocates into the nucleus, and the NF-κB pathway is activated, which further promotes the inflammatory response [36]. Recent studies have shown that lncRNAs can also modulate CIRI pathological processes through regulation of the inflammatory reaction [37]. Studies have indicated that low expression of the lncRNA ANRIL can reduce cerebral infarctioninduced neuronal apoptosis through suppressing the NF-κB signaling pathway [38].…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of lncRNA expression profiles in rats with cerebral ischemia-reperfusion injury after treatment with 20(R)-ginsenoside Rg3

Yang¹,

He²,

Yang³

et al. 2022

J. Integr. Neurosci.

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This study was aimed at investigating the di ferentially expressions of long noncoding RNAs (lncRNAs) and mRNAs in the brains of a middle cerebral artery occlusion/reperfusion (MCAO/R) group and a MCAO/R + 20(R)-Rg3 group. Biological enrichment analysis was performed, and a lncRNA-mRNA coexpression network was constructed, to reveal the targets and pathways of 20(R)-Rg3 involved in the regulation of cerebral ischemia-reperfusion injury (CIRI). The RNA-seq high-throughput sequencing method was employed to detect di ferentially-expressed genes between the groups, which were verified by RT-PCR. Functional enrichment analyses of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were performed to explore the biological functions and relevant pathways. The coexpression network of the screened lncRNAs and mRNAs was built by using Cytoscape so tware. The results identified 77 upregulated lncRNAs, 162 downregulated lncRNAs, 66 upregulated mRNAs and 472 downregulated mRNAs in the MCAO/R + 20(R)-Rg3 group, compared with those in the MCAO/R group. GO enrichment analysis showed that the GO terms were mainly enriched in stimulation response, cellular response, and stress response. KEGG pathways were mainly related to the tumor necrosis factor (TNF), NF-κB, cytokine, and other receptor signaling pathways. In addition, the coexpression analysis between lncRNA and mRNA identified 314 nodes and 515 connections between 6 lncR-NAs and 308 mRNAs, of which 511 were positive and 4 were negative. Among them, ENSRNOG-00000059555 was strongly correlated with AABR07001160.1. This study revealed multiple lncRNAs were involved in the neuroprotection of 20(R)-Rg3 against CIRI and thereby provided new insights into the use of 20(R)-Rg3 as a novel neuro protectant in ischemic stroke management.

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“…Some of these ncRNAs have been shown to be involved in the regulation of inflammation, angiogenesis, and other biological processes related to wound healing. Zhang et al (21) found that the downregulation of lncRNA Gas5 can reduce protein expression of matrix metalloproteinase 7 (MMP-7), cleaved caspase-3 and interleukin 1β (IL-1β), thereby reducing local inflammation. Furthermore, Du et al (22) proposed that lncRNA Mirt2 is a negative regulator of inflammation.…”

Section: Discussionmentioning

confidence: 99%

“…Available at https://dx.doi. org/10.21037/atm- 21 Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the noncommercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.…”

Section: Footnotementioning

confidence: 99%

Comprehensive analysis of lncRNA and miRNA expression profiles and ceRNA network construction in negative pressure wound therapy

Wu¹,

Qin²,

Li³

et al. 2021

Ann Transl Med

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Background: This study aims to explore the molecular mechanism of negative pressure wound therapy (NPWT) at the transcriptome level through whole transcriptome sequencing and biometric analysis.Methods: A rat skin defect model was constructed and randomly divided into a NPWT group and a gauze group. The tissue in the center of the wound was used for whole transcriptome sequencing, and differentially expressed messenger RNAs (DEmRNAs), long noncoding RNAs (DElncRNAs), and microRNAs (DEmiRNAs) were identified between the 2 groups. Quantitative real time-polymerase chain reaction (qRT-PCR) analysis was used to verify the sequencing results. Functional enrichment analysis, pathway analysis, and protein-protein interaction (PPI) network analysis of DEmRNAs were conducted. Through bioinformatics analysis, a lncRNA-associated competing endogenous RNA (ceRNA) network was identified and constructed.Results: We detected 896 DEmRNAs, 1,471 DElncRNAs, and 20 DEmiRNAs between the 2 groups.qRT-PCR verified the sequencing results. Functional analysis showed that DEmRNAs were mainly enriched in immune system processes and the Notch signaling pathway. Protein tyrosine phosphatase receptor type C (PTPRC) and signal transducer and activator of transcription 1 (STAT1) were the central hub nodes in the PPI analysis. The ceRNA network contained 11 mRNAs, 15 lncRNAs, and 4 miRNAs. Conclusions:We identified several DEmRNAs, DElncRNAs, and DEmiRNAs between the NPWT treatment group and the control group. These findings may provide new insights into the pathophysiological mechanism of NPWT and wound healing.

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Downregulation of LncRNA Gas5 inhibits apoptosis and inflammation after spinal cord ischemia-reperfusion in rats

Cited by 23 publications

References 36 publications

The Roles of Matrix Metalloproteinase 7 in Spinal Cord Ischemia- Reperfusion Injury in Rats

The Roles of Matrix Metalloproteinase 7 in Spinal Cord Ischemia- Reperfusion Injury in Rats

Comprehensive analysis of lncRNA expression profiles in rats with cerebral ischemia-reperfusion injury after treatment with 20(R)-ginsenoside Rg3

Comprehensive analysis of lncRNA and miRNA expression profiles and ceRNA network construction in negative pressure wound therapy

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