CircHivep2 contributes to microglia activation and inflammation via miR‐181a‐5p/SOCS2 signalling in mice with kainic acid‐induced epileptic seizures
Epilepsy is a chronic brain disease characterized by recurrent seizures. Circular RNA (circRNA) is a novel family of endogenous non‐coding RNAs that have been proposed to regulate gene expression. However, there is a lack of data on the role of circRNA in epilepsy. In this study, the circRNA profile...
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| Veröffentlicht in: | Journal of cellular and molecular medicine 2020-11, Vol.24 (22), p.12980-12993 |
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| creator | Xiaoying, Gao Guo, Mian Jie, Liu Yanmei, Zhu Ying, Cui Shengjie, Shu Haiyan, Gou Feixiang, Sun Sihua, Qi Jiahang, Sun |
| description | Epilepsy is a chronic brain disease characterized by recurrent seizures. Circular RNA (circRNA) is a novel family of endogenous non‐coding RNAs that have been proposed to regulate gene expression. However, there is a lack of data on the role of circRNA in epilepsy. In this study, the circRNA profiles were evaluated by microarray analysis. In total, 627 circRNAs were up‐regulated, whereas 892 were down‐regulated in the hippocampus in mice with kainic acid (KA)‐induced epileptic seizures compared with control. The expression of circHivep2 was significantly down‐regulated in hippocampus tissues of mice with KA‐induced epileptic seizures and BV‐2 microglia cells upon KA treatment. Bioinformatics analysis predicted that circHivep2 interacts with miR‐181a‐5p to regulate SOCS2 expression, which was validated using a dual‐luciferase reporter assay. Moreover, overexpression of circHivep2 significantly inhibited KA‐induced microglial activation and the expression of inflammatory factors in vitro, which was blocked by miR‐181a‐5p, whereas circHivep2 knockdown further induced microglia cell activation and the release of pro‐inflammatory proteins in BV‐2 microglia cells after KA treatment. The application of circHivep2+ exosomes derived from adipose‐derived stem cells (ADSCs) exerted significant beneficial effects on the behavioural seizure scores of mice with KA‐induced epilepsy compared to control exosomes. The circHivep2+ exosomes also inhibited microglial activation, the expression of inflammatory factors, and the miR‐181a‐5p/SOCS2 axis in vivo. Our results suggest that circHivep2 regulates microglia activation in the progression of epilepsy by interfering with miR‐181a‐5p to promote SOCS2 expression, indicating that circHivep2 may serve as a therapeutic tool to prevent the development of epilepsy. |
| doi_str_mv | 10.1111/jcmm.15894 |
| format | Article |
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Circular RNA (circRNA) is a novel family of endogenous non‐coding RNAs that have been proposed to regulate gene expression. However, there is a lack of data on the role of circRNA in epilepsy. In this study, the circRNA profiles were evaluated by microarray analysis. In total, 627 circRNAs were up‐regulated, whereas 892 were down‐regulated in the hippocampus in mice with kainic acid (KA)‐induced epileptic seizures compared with control. The expression of circHivep2 was significantly down‐regulated in hippocampus tissues of mice with KA‐induced epileptic seizures and BV‐2 microglia cells upon KA treatment. Bioinformatics analysis predicted that circHivep2 interacts with miR‐181a‐5p to regulate SOCS2 expression, which was validated using a dual‐luciferase reporter assay. Moreover, overexpression of circHivep2 significantly inhibited KA‐induced microglial activation and the expression of inflammatory factors in vitro, which was blocked by miR‐181a‐5p, whereas circHivep2 knockdown further induced microglia cell activation and the release of pro‐inflammatory proteins in BV‐2 microglia cells after KA treatment. The application of circHivep2+ exosomes derived from adipose‐derived stem cells (ADSCs) exerted significant beneficial effects on the behavioural seizure scores of mice with KA‐induced epilepsy compared to control exosomes. The circHivep2+ exosomes also inhibited microglial activation, the expression of inflammatory factors, and the miR‐181a‐5p/SOCS2 axis in vivo. Our results suggest that circHivep2 regulates microglia activation in the progression of epilepsy by interfering with miR‐181a‐5p to promote SOCS2 expression, indicating that circHivep2 may serve as a therapeutic tool to prevent the development of epilepsy.</description><identifier>ISSN: 1582-1838</identifier><identifier>EISSN: 1582-4934</identifier><identifier>DOI: 10.1111/jcmm.15894</identifier><identifier>PMID: 33002329</identifier><language>eng</language><publisher>England: John Wiley & Sons, Inc</publisher><subject>Acids ; Bioinformatics ; Brain ; Cell activation ; Circular RNA ; circular RNAs ; Convulsions & seizures ; DNA methylation ; DNA microarrays ; Epilepsy ; Exosomes ; Gene expression ; Hippocampus ; Inflammation ; inflammatory response ; Kainic acid ; Laboratory animals ; Microglia ; microglia activation ; MicroRNAs ; miR‐181a‐5p ; Non-coding RNA ; Original ; Proteins ; Ribonucleic acid ; RNA ; Seizures ; Stem cell transplantation ; Stem cells</subject><ispartof>Journal of cellular and molecular medicine, 2020-11, Vol.24 (22), p.12980-12993</ispartof><rights>2020 The Authors. published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd</rights><rights>2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.</rights><rights>2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4484-c2e05afed09df541712fc0db353de1a4cc13a1999ee72eb0cf9efe3df1a0e71d3</citedby><cites>FETCH-LOGICAL-c4484-c2e05afed09df541712fc0db353de1a4cc13a1999ee72eb0cf9efe3df1a0e71d3</cites><orcidid>0000-0002-7945-0244</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7701587/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7701587/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,1417,11562,27924,27925,45574,45575,46052,46476,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33002329$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Xiaoying, Gao</creatorcontrib><creatorcontrib>Guo, Mian</creatorcontrib><creatorcontrib>Jie, Liu</creatorcontrib><creatorcontrib>Yanmei, Zhu</creatorcontrib><creatorcontrib>Ying, Cui</creatorcontrib><creatorcontrib>Shengjie, Shu</creatorcontrib><creatorcontrib>Haiyan, Gou</creatorcontrib><creatorcontrib>Feixiang, Sun</creatorcontrib><creatorcontrib>Sihua, Qi</creatorcontrib><creatorcontrib>Jiahang, Sun</creatorcontrib><title>CircHivep2 contributes to microglia activation and inflammation via miR‐181a‐5p/SOCS2 signalling in mice with kainic acid‐induced epileptic seizures</title><title>Journal of cellular and molecular medicine</title><addtitle>J Cell Mol Med</addtitle><description>Epilepsy is a chronic brain disease characterized by recurrent seizures. Circular RNA (circRNA) is a novel family of endogenous non‐coding RNAs that have been proposed to regulate gene expression. However, there is a lack of data on the role of circRNA in epilepsy. In this study, the circRNA profiles were evaluated by microarray analysis. In total, 627 circRNAs were up‐regulated, whereas 892 were down‐regulated in the hippocampus in mice with kainic acid (KA)‐induced epileptic seizures compared with control. The expression of circHivep2 was significantly down‐regulated in hippocampus tissues of mice with KA‐induced epileptic seizures and BV‐2 microglia cells upon KA treatment. Bioinformatics analysis predicted that circHivep2 interacts with miR‐181a‐5p to regulate SOCS2 expression, which was validated using a dual‐luciferase reporter assay. Moreover, overexpression of circHivep2 significantly inhibited KA‐induced microglial activation and the expression of inflammatory factors in vitro, which was blocked by miR‐181a‐5p, whereas circHivep2 knockdown further induced microglia cell activation and the release of pro‐inflammatory proteins in BV‐2 microglia cells after KA treatment. The application of circHivep2+ exosomes derived from adipose‐derived stem cells (ADSCs) exerted significant beneficial effects on the behavioural seizure scores of mice with KA‐induced epilepsy compared to control exosomes. The circHivep2+ exosomes also inhibited microglial activation, the expression of inflammatory factors, and the miR‐181a‐5p/SOCS2 axis in vivo. Our results suggest that circHivep2 regulates microglia activation in the progression of epilepsy by interfering with miR‐181a‐5p to promote SOCS2 expression, indicating that circHivep2 may serve as a therapeutic tool to prevent the development of epilepsy.</description><subject>Acids</subject><subject>Bioinformatics</subject><subject>Brain</subject><subject>Cell activation</subject><subject>Circular RNA</subject><subject>circular RNAs</subject><subject>Convulsions & seizures</subject><subject>DNA methylation</subject><subject>DNA microarrays</subject><subject>Epilepsy</subject><subject>Exosomes</subject><subject>Gene expression</subject><subject>Hippocampus</subject><subject>Inflammation</subject><subject>inflammatory response</subject><subject>Kainic acid</subject><subject>Laboratory animals</subject><subject>Microglia</subject><subject>microglia activation</subject><subject>MicroRNAs</subject><subject>miR‐181a‐5p</subject><subject>Non-coding 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activation and inflammation via miR‐181a‐5p/SOCS2 signalling in mice with kainic acid‐induced epileptic seizures</atitle><jtitle>Journal of cellular and molecular medicine</jtitle><addtitle>J Cell Mol Med</addtitle><date>2020-11</date><risdate>2020</risdate><volume>24</volume><issue>22</issue><spage>12980</spage><epage>12993</epage><pages>12980-12993</pages><issn>1582-1838</issn><eissn>1582-4934</eissn><abstract>Epilepsy is a chronic brain disease characterized by recurrent seizures. Circular RNA (circRNA) is a novel family of endogenous non‐coding RNAs that have been proposed to regulate gene expression. However, there is a lack of data on the role of circRNA in epilepsy. In this study, the circRNA profiles were evaluated by microarray analysis. In total, 627 circRNAs were up‐regulated, whereas 892 were down‐regulated in the hippocampus in mice with kainic acid (KA)‐induced epileptic seizures compared with control. The expression of circHivep2 was significantly down‐regulated in hippocampus tissues of mice with KA‐induced epileptic seizures and BV‐2 microglia cells upon KA treatment. Bioinformatics analysis predicted that circHivep2 interacts with miR‐181a‐5p to regulate SOCS2 expression, which was validated using a dual‐luciferase reporter assay. Moreover, overexpression of circHivep2 significantly inhibited KA‐induced microglial activation and the expression of inflammatory factors in vitro, which was blocked by miR‐181a‐5p, whereas circHivep2 knockdown further induced microglia cell activation and the release of pro‐inflammatory proteins in BV‐2 microglia cells after KA treatment. The application of circHivep2+ exosomes derived from adipose‐derived stem cells (ADSCs) exerted significant beneficial effects on the behavioural seizure scores of mice with KA‐induced epilepsy compared to control exosomes. The circHivep2+ exosomes also inhibited microglial activation, the expression of inflammatory factors, and the miR‐181a‐5p/SOCS2 axis in vivo. Our results suggest that circHivep2 regulates microglia activation in the progression of epilepsy by interfering with miR‐181a‐5p to promote SOCS2 expression, indicating that circHivep2 may serve as a therapeutic tool to prevent the development of epilepsy.</abstract><cop>England</cop><pub>John Wiley & Sons, Inc</pub><pmid>33002329</pmid><doi>10.1111/jcmm.15894</doi><tpages>14</tpages><orcidid>https://orcid.org/0000-0002-7945-0244</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Acids Bioinformatics Brain Cell activation Circular RNA circular RNAs Convulsions & seizures DNA methylation DNA microarrays Epilepsy Exosomes Gene expression Hippocampus Inflammation inflammatory response Kainic acid Laboratory animals Microglia microglia activation MicroRNAs miR‐181a‐5p Non-coding RNA Original Proteins Ribonucleic acid RNA Seizures Stem cell transplantation Stem cells |
| title | CircHivep2 contributes to microglia activation and inflammation via miR‐181a‐5p/SOCS2 signalling in mice with kainic acid‐induced epileptic seizures |
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