The Monocyte-Derived Exosomal CLMAT3 Activates the CtBP2-p300-NF-κB Transcriptional Complex to Induce Proinflammatory Cytokines in ALI
Monocytes and macrophages are the two major cell types involved in innate immunity. Exosomes act as signaling molecules to regulate cell-to-cell communication by releasing proteins, mRNAs, microRNAs (miRNAs), and long noncoding RNAs (lncRNAs). However, it is still unclear whether monocyte-derived ex...
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| Format: | Article |
| Language: | English |
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Elsevier
2020-09-01
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| Series: | Molecular Therapy: Nucleic Acids |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2162253120302298 |
| _version_ | 1818157215425495040 |
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| author | Zhi Chen Wei-Hua Dong Zhong-Min Qiu Qiu-Gen Li |
| author_facet | Zhi Chen Wei-Hua Dong Zhong-Min Qiu Qiu-Gen Li |
| author_sort | Zhi Chen |
| collection | DOAJ |
| description | Monocytes and macrophages are the two major cell types involved in innate immunity. Exosomes act as signaling molecules to regulate cell-to-cell communication by releasing proteins, mRNAs, microRNAs (miRNAs), and long noncoding RNAs (lncRNAs). However, it is still unclear whether monocyte-derived exosomes are involved in the communication between monocytes and macrophages. In this study, we analyzed the differentially expressed lncRNA profiles in monocytes isolated from blood samples of healthy controls and acute lung injury (ALI) patients. We focused our study on investigating the signaling downstream of CLMAT3 (colorectal liver metastasis-associated transcript 3), a lncRNA that regulated proinflammatory cytokine genes. We revealed that CLMAT3 specifically targeted CtBP2 (C-terminal binding protein 2) and repressed its expression. Elevated CtBP2 acted as a coactivator to assemble a transcriptional complex with histone acetyltransferase p300 and NF-κB (nuclear factor κB) subunits. In vitro coculture and in vivo injection of ALI monocyte-derived exosomes increased the production of proinflammatory cytokines. Importantly, the administration of two CtBP2 inhibitors, NSC95397 and MTOB, could significantly reverse CtBP2-mediated transactivation. Collectively, our results support a model in which monocyte-derived exosomal CLMAT3 activates the CtBP2-p300-NF-κB complex to induce proinflammatory cytokines, thus contributing to the pathogenesis of ALI. |
| first_indexed | 2024-12-11T15:10:39Z |
| format | Article |
| id | doaj.art-d2363e74f67943fe997b94a70ec6cda2 |
| institution | Directory Open Access Journal |
| issn | 2162-2531 |
| language | English |
| last_indexed | 2024-12-11T15:10:39Z |
| publishDate | 2020-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Nucleic Acids |
| spelling | doaj.art-d2363e74f67943fe997b94a70ec6cda22022-12-22T01:00:46ZengElsevierMolecular Therapy: Nucleic Acids2162-25312020-09-012111001110The Monocyte-Derived Exosomal CLMAT3 Activates the CtBP2-p300-NF-κB Transcriptional Complex to Induce Proinflammatory Cytokines in ALIZhi Chen0Wei-Hua Dong1Zhong-Min Qiu2Qiu-Gen Li3Department of Critical Care Medicine, Jiangxi Provincial People’s Hospital Affiliated to Nanchang University, Nanchang 330006, Jiangxi, China; Department of Pulmonary and Critical Care Medicine, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, ChinaDepartment of Critical Care Medicine, Jiangxi Provincial People’s Hospital Affiliated to Nanchang University, Nanchang 330006, Jiangxi, ChinaDepartment of Pulmonary and Critical Care Medicine, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, ChinaDepartment of Pulmonary and Critical Care Medicine, Jiangxi Provincial People’s Hospital Affiliated to Nanchang University, Nanchang 330006, Jiangxi, China; Corresponding author: Qiu-Gen Li, Department of Pulmonary and Critical Care Medicine, Jiangxi Provincial People’s Hospital Affiliated to Nanchang University, Nanchang 330006, Jiangxi, China.Monocytes and macrophages are the two major cell types involved in innate immunity. Exosomes act as signaling molecules to regulate cell-to-cell communication by releasing proteins, mRNAs, microRNAs (miRNAs), and long noncoding RNAs (lncRNAs). However, it is still unclear whether monocyte-derived exosomes are involved in the communication between monocytes and macrophages. In this study, we analyzed the differentially expressed lncRNA profiles in monocytes isolated from blood samples of healthy controls and acute lung injury (ALI) patients. We focused our study on investigating the signaling downstream of CLMAT3 (colorectal liver metastasis-associated transcript 3), a lncRNA that regulated proinflammatory cytokine genes. We revealed that CLMAT3 specifically targeted CtBP2 (C-terminal binding protein 2) and repressed its expression. Elevated CtBP2 acted as a coactivator to assemble a transcriptional complex with histone acetyltransferase p300 and NF-κB (nuclear factor κB) subunits. In vitro coculture and in vivo injection of ALI monocyte-derived exosomes increased the production of proinflammatory cytokines. Importantly, the administration of two CtBP2 inhibitors, NSC95397 and MTOB, could significantly reverse CtBP2-mediated transactivation. Collectively, our results support a model in which monocyte-derived exosomal CLMAT3 activates the CtBP2-p300-NF-κB complex to induce proinflammatory cytokines, thus contributing to the pathogenesis of ALI.http://www.sciencedirect.com/science/article/pii/S2162253120302298CLMAT3CtBP2p300NF-κBacute lung injuryexosome |
| spellingShingle | Zhi Chen Wei-Hua Dong Zhong-Min Qiu Qiu-Gen Li The Monocyte-Derived Exosomal CLMAT3 Activates the CtBP2-p300-NF-κB Transcriptional Complex to Induce Proinflammatory Cytokines in ALI Molecular Therapy: Nucleic Acids CLMAT3 CtBP2 p300 NF-κB acute lung injury exosome |
| title | The Monocyte-Derived Exosomal CLMAT3 Activates the CtBP2-p300-NF-κB Transcriptional Complex to Induce Proinflammatory Cytokines in ALI |
| title_full | The Monocyte-Derived Exosomal CLMAT3 Activates the CtBP2-p300-NF-κB Transcriptional Complex to Induce Proinflammatory Cytokines in ALI |
| title_fullStr | The Monocyte-Derived Exosomal CLMAT3 Activates the CtBP2-p300-NF-κB Transcriptional Complex to Induce Proinflammatory Cytokines in ALI |
| title_full_unstemmed | The Monocyte-Derived Exosomal CLMAT3 Activates the CtBP2-p300-NF-κB Transcriptional Complex to Induce Proinflammatory Cytokines in ALI |
| title_short | The Monocyte-Derived Exosomal CLMAT3 Activates the CtBP2-p300-NF-κB Transcriptional Complex to Induce Proinflammatory Cytokines in ALI |
| title_sort | monocyte derived exosomal clmat3 activates the ctbp2 p300 nf κb transcriptional complex to induce proinflammatory cytokines in ali |
| topic | CLMAT3 CtBP2 p300 NF-κB acute lung injury exosome |
| url | http://www.sciencedirect.com/science/article/pii/S2162253120302298 |
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