SNHG15 is a negative regulator of inflammation by mediating TRAF2 ubiquitination in stroke-induced immunosuppression
Abstract Background Abnormal expression of long noncoding RNAs (lncRNAs) has been reported in the acute stage of acute ischemic stroke (AIS). This study aimed to explore differential lncRNA expression in the subpopulations of peripheral blood mononuclear cells (PBMCs) from AIS patients and further e...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-01-01
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| Series: | Journal of Neuroinflammation |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12974-021-02372-z |
| _version_ | 1818964019968475136 |
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| author | Huiling Sun Shuo Li Zhaohan Xu Chengfang Liu Pengyu Gong Qiwen Deng Fuling Yan |
| author_facet | Huiling Sun Shuo Li Zhaohan Xu Chengfang Liu Pengyu Gong Qiwen Deng Fuling Yan |
| author_sort | Huiling Sun |
| collection | DOAJ |
| description | Abstract Background Abnormal expression of long noncoding RNAs (lncRNAs) has been reported in the acute stage of acute ischemic stroke (AIS). This study aimed to explore differential lncRNA expression in the subpopulations of peripheral blood mononuclear cells (PBMCs) from AIS patients and further evaluate its underlying mechanisms in stroke-induced immunosuppression. Methods We reanalyzed lncRNA microarray data and investigated abnormally expressed lncRNAs in the subpopulations of PBMCs by magnetic cell sorting and real-time quantitative PCR. The potential mechanism of small nucleolar RNA host gene 15 (SNHG15) was explored through in vitro and in vivo approaches. Results The stroke-induced SNHG15 acted as a checkpoint to inhibit peripheral inflammatory responses. Functional studies showed that SNHG15 promoted M2 macrophage polarization. Mechanistically, SNHG15 expression was dysregulated through the Janus kinase (JAK)-signal transducer and activator of transcription 6 (STAT6) signaling pathway. SNHG15, localized in the cytoplasm, interfered with K63-linked ubiquitination of tumor necrosis factor receptor-associated factor 2 and thereby repressed the activation of mitogen-activated protein kinase and nuclear factor kappa-B signaling pathways and prevented the production of proinflammatory cytokines. Administration of an adenovirus targeting SNHG15 improved stroke-induced immunosuppression in mice. Conclusions This study identified SNHG15 as a negative regulator of inflammation in stroke-induced immunosuppression, suggesting it as a novel biomarker and therapeutic target in stroke-associated infection. Trial registration ClinicalTrials.gov NCT04175691. Registered November 25, 2019, https://www.clinicaltrials.gov/ct2/show/NCT04175691 . |
| first_indexed | 2024-12-20T12:54:28Z |
| format | Article |
| id | doaj.art-0c66b96b734a4763a009b452b5bb8393 |
| institution | Directory Open Access Journal |
| issn | 1742-2094 |
| language | English |
| last_indexed | 2024-12-20T12:54:28Z |
| publishDate | 2022-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neuroinflammation |
| spelling | doaj.art-0c66b96b734a4763a009b452b5bb83932022-12-21T19:40:05ZengBMCJournal of Neuroinflammation1742-20942022-01-0119111510.1186/s12974-021-02372-zSNHG15 is a negative regulator of inflammation by mediating TRAF2 ubiquitination in stroke-induced immunosuppressionHuiling Sun0Shuo Li1Zhaohan Xu2Chengfang Liu3Pengyu Gong4Qiwen Deng5Fuling Yan6General Clinical Research Center, Nanjing First Hospital, Nanjing Medical UniversityDepartment of Neurology, Affiliated ZhongDa Hospital, School of Medicine, Southeast UniversityDepartment of Neurology, Nanjing First Hospital, Nanjing Medical UniversityDepartment of Neurology, Nanjing First Hospital, Nanjing Medical UniversityDepartment of Neurology, Nanjing First Hospital, Nanjing Medical UniversityDepartment of Neurology, Nanjing First Hospital, Nanjing Medical UniversityDepartment of Neurology, Affiliated ZhongDa Hospital, School of Medicine, Southeast UniversityAbstract Background Abnormal expression of long noncoding RNAs (lncRNAs) has been reported in the acute stage of acute ischemic stroke (AIS). This study aimed to explore differential lncRNA expression in the subpopulations of peripheral blood mononuclear cells (PBMCs) from AIS patients and further evaluate its underlying mechanisms in stroke-induced immunosuppression. Methods We reanalyzed lncRNA microarray data and investigated abnormally expressed lncRNAs in the subpopulations of PBMCs by magnetic cell sorting and real-time quantitative PCR. The potential mechanism of small nucleolar RNA host gene 15 (SNHG15) was explored through in vitro and in vivo approaches. Results The stroke-induced SNHG15 acted as a checkpoint to inhibit peripheral inflammatory responses. Functional studies showed that SNHG15 promoted M2 macrophage polarization. Mechanistically, SNHG15 expression was dysregulated through the Janus kinase (JAK)-signal transducer and activator of transcription 6 (STAT6) signaling pathway. SNHG15, localized in the cytoplasm, interfered with K63-linked ubiquitination of tumor necrosis factor receptor-associated factor 2 and thereby repressed the activation of mitogen-activated protein kinase and nuclear factor kappa-B signaling pathways and prevented the production of proinflammatory cytokines. Administration of an adenovirus targeting SNHG15 improved stroke-induced immunosuppression in mice. Conclusions This study identified SNHG15 as a negative regulator of inflammation in stroke-induced immunosuppression, suggesting it as a novel biomarker and therapeutic target in stroke-associated infection. Trial registration ClinicalTrials.gov NCT04175691. Registered November 25, 2019, https://www.clinicaltrials.gov/ct2/show/NCT04175691 .https://doi.org/10.1186/s12974-021-02372-zLong noncoding RNAIschemic strokeSNHG15ImmunosuppressionTRAF2 |
| spellingShingle | Huiling Sun Shuo Li Zhaohan Xu Chengfang Liu Pengyu Gong Qiwen Deng Fuling Yan SNHG15 is a negative regulator of inflammation by mediating TRAF2 ubiquitination in stroke-induced immunosuppression Journal of Neuroinflammation Long noncoding RNA Ischemic stroke SNHG15 Immunosuppression TRAF2 |
| title | SNHG15 is a negative regulator of inflammation by mediating TRAF2 ubiquitination in stroke-induced immunosuppression |
| title_full | SNHG15 is a negative regulator of inflammation by mediating TRAF2 ubiquitination in stroke-induced immunosuppression |
| title_fullStr | SNHG15 is a negative regulator of inflammation by mediating TRAF2 ubiquitination in stroke-induced immunosuppression |
| title_full_unstemmed | SNHG15 is a negative regulator of inflammation by mediating TRAF2 ubiquitination in stroke-induced immunosuppression |
| title_short | SNHG15 is a negative regulator of inflammation by mediating TRAF2 ubiquitination in stroke-induced immunosuppression |
| title_sort | snhg15 is a negative regulator of inflammation by mediating traf2 ubiquitination in stroke induced immunosuppression |
| topic | Long noncoding RNA Ischemic stroke SNHG15 Immunosuppression TRAF2 |
| url | https://doi.org/10.1186/s12974-021-02372-z |
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