Characterization of Long Non-Coding RNAs in Systemic Sclerosis Monocytes: A Potential Role for PSMB8-AS1 in Altered Cytokine Secretion
Systemic sclerosis (SSc) is a chronic autoimmune disease mainly affecting the connective tissue. In SSc patients, monocytes are increased in circulation, infiltrate affected tissues, and show a pro-inflammatory activation status, including the so-called interferon (IFN) signature. We previously demo...
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2021-04-01
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| Series: | International Journal of Molecular Sciences |
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| author | Nila H. Servaas Barbara Mariotti Maarten van der Kroef Catharina G. K. Wichers Aridaman Pandit Flavia Bazzoni Timothy R. D. J. Radstake Marzia Rossato |
| author_facet | Nila H. Servaas Barbara Mariotti Maarten van der Kroef Catharina G. K. Wichers Aridaman Pandit Flavia Bazzoni Timothy R. D. J. Radstake Marzia Rossato |
| author_sort | Nila H. Servaas |
| collection | DOAJ |
| description | Systemic sclerosis (SSc) is a chronic autoimmune disease mainly affecting the connective tissue. In SSc patients, monocytes are increased in circulation, infiltrate affected tissues, and show a pro-inflammatory activation status, including the so-called interferon (IFN) signature. We previously demonstrated that the dysregulation of the IFN response in SSc monocytes is sustained by altered epigenetic factors as well as by upregulation of the long non-coding RNA (lncRNA) NRIR. Considering the enormously diverse molecular functions of lncRNAs in immune regulation, the present study investigated the genome-wide profile of lncRNAs in SSc monocytes, with the aim to further unravel their possible role in monocyte dysregulation and disease pathogenesis. Transcriptomic data from two independent cohorts of SSc patients identified 886 lncRNAs with an altered expression in SSc monocytes. Differentially expressed lncRNAs were correlated with neighboring protein coding genes implicated in the regulation of IFN responses and apoptotic signaling in SSc monocytes. In parallel, gene co-expression network analysis identified the lncRNA PSMB8-AS1 as a top-ranking hub gene in co-expression modules implicated in cell activation and response to viral and external stimuli. Functional characterization of PSMB8-AS1 in monocytes demonstrated that this lncRNA is involved in the secretion of IL-6 and TNFα, two pivotal pro-inflammatory cytokines altered in the circulation of SSc patients and associated with fibrosis and disease severity. Collectively, our data showed that lncRNAs are linked to monocyte dysregulation in SSc, and highlight their potential contribution to disease pathogenesis. |
| first_indexed | 2024-03-10T12:06:05Z |
| format | Article |
| id | doaj.art-c807676decdc4106bbea270cd647b540 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T12:06:05Z |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-c807676decdc4106bbea270cd647b5402023-11-21T16:37:59ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-04-01229436510.3390/ijms22094365Characterization of Long Non-Coding RNAs in Systemic Sclerosis Monocytes: A Potential Role for PSMB8-AS1 in Altered Cytokine SecretionNila H. Servaas0Barbara Mariotti1Maarten van der Kroef2Catharina G. K. Wichers3Aridaman Pandit4Flavia Bazzoni5Timothy R. D. J. Radstake6Marzia Rossato7Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, 3584 CX Utrecht, The NetherlandsDivision of General Pathology, Department of Medicine, University of Verona, 37134 Verona, ItalyCenter for Translational Immunology, University Medical Center Utrecht, Utrecht University, 3584 CX Utrecht, The NetherlandsCenter for Translational Immunology, University Medical Center Utrecht, Utrecht University, 3584 CX Utrecht, The NetherlandsCenter for Translational Immunology, University Medical Center Utrecht, Utrecht University, 3584 CX Utrecht, The NetherlandsDivision of General Pathology, Department of Medicine, University of Verona, 37134 Verona, ItalyCenter for Translational Immunology, University Medical Center Utrecht, Utrecht University, 3584 CX Utrecht, The NetherlandsDepartment of Biotechnology, University of Verona, 37134 Verona, ItalySystemic sclerosis (SSc) is a chronic autoimmune disease mainly affecting the connective tissue. In SSc patients, monocytes are increased in circulation, infiltrate affected tissues, and show a pro-inflammatory activation status, including the so-called interferon (IFN) signature. We previously demonstrated that the dysregulation of the IFN response in SSc monocytes is sustained by altered epigenetic factors as well as by upregulation of the long non-coding RNA (lncRNA) NRIR. Considering the enormously diverse molecular functions of lncRNAs in immune regulation, the present study investigated the genome-wide profile of lncRNAs in SSc monocytes, with the aim to further unravel their possible role in monocyte dysregulation and disease pathogenesis. Transcriptomic data from two independent cohorts of SSc patients identified 886 lncRNAs with an altered expression in SSc monocytes. Differentially expressed lncRNAs were correlated with neighboring protein coding genes implicated in the regulation of IFN responses and apoptotic signaling in SSc monocytes. In parallel, gene co-expression network analysis identified the lncRNA PSMB8-AS1 as a top-ranking hub gene in co-expression modules implicated in cell activation and response to viral and external stimuli. Functional characterization of PSMB8-AS1 in monocytes demonstrated that this lncRNA is involved in the secretion of IL-6 and TNFα, two pivotal pro-inflammatory cytokines altered in the circulation of SSc patients and associated with fibrosis and disease severity. Collectively, our data showed that lncRNAs are linked to monocyte dysregulation in SSc, and highlight their potential contribution to disease pathogenesis.https://www.mdpi.com/1422-0067/22/9/4365systemic sclerosismonocyteslong non-coding RNAautoimmuneco-expression network |
| spellingShingle | Nila H. Servaas Barbara Mariotti Maarten van der Kroef Catharina G. K. Wichers Aridaman Pandit Flavia Bazzoni Timothy R. D. J. Radstake Marzia Rossato Characterization of Long Non-Coding RNAs in Systemic Sclerosis Monocytes: A Potential Role for PSMB8-AS1 in Altered Cytokine Secretion International Journal of Molecular Sciences systemic sclerosis monocytes long non-coding RNA autoimmune co-expression network |
| title | Characterization of Long Non-Coding RNAs in Systemic Sclerosis Monocytes: A Potential Role for PSMB8-AS1 in Altered Cytokine Secretion |
| title_full | Characterization of Long Non-Coding RNAs in Systemic Sclerosis Monocytes: A Potential Role for PSMB8-AS1 in Altered Cytokine Secretion |
| title_fullStr | Characterization of Long Non-Coding RNAs in Systemic Sclerosis Monocytes: A Potential Role for PSMB8-AS1 in Altered Cytokine Secretion |
| title_full_unstemmed | Characterization of Long Non-Coding RNAs in Systemic Sclerosis Monocytes: A Potential Role for PSMB8-AS1 in Altered Cytokine Secretion |
| title_short | Characterization of Long Non-Coding RNAs in Systemic Sclerosis Monocytes: A Potential Role for PSMB8-AS1 in Altered Cytokine Secretion |
| title_sort | characterization of long non coding rnas in systemic sclerosis monocytes a potential role for psmb8 as1 in altered cytokine secretion |
| topic | systemic sclerosis monocytes long non-coding RNA autoimmune co-expression network |
| url | https://www.mdpi.com/1422-0067/22/9/4365 |
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