Differential Proteomic Analysis of Astrocytes and Astrocytes-Derived Extracellular Vesicles from Control and Rai Knockout Mice: Insights into the Mechanisms of Neuroprotection
Reactive astrocytes are a hallmark of neurodegenerative disease including multiple sclerosis. It is widely accepted that astrocytes may adopt alternative phenotypes depending on a combination of environmental cues and intrinsic features in a highly plastic and heterogeneous manner. However, we still...
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MDPI AG
2021-07-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/15/7933 |
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| author | Tommaso Montecchi Enxhi Shaba Domiziana De Tommaso Fabrizio Di Giuseppe Stefania Angelucci Luca Bini Claudia Landi Cosima Tatiana Baldari Cristina Ulivieri |
| author_facet | Tommaso Montecchi Enxhi Shaba Domiziana De Tommaso Fabrizio Di Giuseppe Stefania Angelucci Luca Bini Claudia Landi Cosima Tatiana Baldari Cristina Ulivieri |
| author_sort | Tommaso Montecchi |
| collection | DOAJ |
| description | Reactive astrocytes are a hallmark of neurodegenerative disease including multiple sclerosis. It is widely accepted that astrocytes may adopt alternative phenotypes depending on a combination of environmental cues and intrinsic features in a highly plastic and heterogeneous manner. However, we still lack a full understanding of signals and associated signaling pathways driving astrocyte reaction and of the mechanisms by which they drive disease. We have previously shown in the experimental autoimmune encephalomyelitis mouse model that deficiency of the molecular adaptor Rai reduces disease severity and demyelination. Moreover, using primary mouse astrocytes, we showed that Rai contributes to the generation of a pro-inflammatory central nervous system (CNS) microenvironment through the production of nitric oxide and IL-6 and by impairing CD39 activity in response to soluble factors released by encephalitogenic T cells. Here, we investigated the impact of Rai expression on astrocyte function both under basal conditions and in response to IL-17 treatment using a proteomic approach. We found that astrocytes and astrocyte-derived extracellular vesicles contain a set of proteins, to which Rai contributes, that are involved in the regulation of oligodendrocyte differentiation and myelination, nitrogen metabolism, and oxidative stress. The HIF-1α pathway and cellular energetic metabolism were the most statistically relevant molecular pathways and were related to ENOA and HSP70 dysregulation. |
| first_indexed | 2024-03-10T09:14:57Z |
| format | Article |
| id | doaj.art-6a5ff059b5a34705bdf834a23fb02439 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T09:14:57Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-6a5ff059b5a34705bdf834a23fb024392023-11-22T05:40:41ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-07-012215793310.3390/ijms22157933Differential Proteomic Analysis of Astrocytes and Astrocytes-Derived Extracellular Vesicles from Control and Rai Knockout Mice: Insights into the Mechanisms of NeuroprotectionTommaso Montecchi0Enxhi Shaba1Domiziana De Tommaso2Fabrizio Di Giuseppe3Stefania Angelucci4Luca Bini5Claudia Landi6Cosima Tatiana Baldari7Cristina Ulivieri8Department of Life Sciences, University of Siena, Via Aldo Moro, 2, 53100 Siena, ItalyFunctional Proteomics Laboratory, Department of Life Sciences, University of Siena, Via Aldo Moro, 2, 53100 Siena, ItalyDepartment of Life Sciences, University of Siena, Via Aldo Moro, 2, 53100 Siena, ItalyCentre of Advanced Studies and Technoloy, Dentistry and Biotechnology and Proteomics Unit, Department Medical, Oral & Biotechnological Sciences, “G. d’Annunzio”, University of Chieti-Pescara, Via dei Vestini, 31, 66100 Chieti, ItalyCentre of Advanced Studies and Technoloy, Dentistry and Biotechnology and Proteomics Unit, Department Medical, Oral & Biotechnological Sciences, “G. d’Annunzio”, University of Chieti-Pescara, Via dei Vestini, 31, 66100 Chieti, ItalyFunctional Proteomics Laboratory, Department of Life Sciences, University of Siena, Via Aldo Moro, 2, 53100 Siena, ItalyFunctional Proteomics Laboratory, Department of Life Sciences, University of Siena, Via Aldo Moro, 2, 53100 Siena, ItalyDepartment of Life Sciences, University of Siena, Via Aldo Moro, 2, 53100 Siena, ItalyDepartment of Life Sciences, University of Siena, Via Aldo Moro, 2, 53100 Siena, ItalyReactive astrocytes are a hallmark of neurodegenerative disease including multiple sclerosis. It is widely accepted that astrocytes may adopt alternative phenotypes depending on a combination of environmental cues and intrinsic features in a highly plastic and heterogeneous manner. However, we still lack a full understanding of signals and associated signaling pathways driving astrocyte reaction and of the mechanisms by which they drive disease. We have previously shown in the experimental autoimmune encephalomyelitis mouse model that deficiency of the molecular adaptor Rai reduces disease severity and demyelination. Moreover, using primary mouse astrocytes, we showed that Rai contributes to the generation of a pro-inflammatory central nervous system (CNS) microenvironment through the production of nitric oxide and IL-6 and by impairing CD39 activity in response to soluble factors released by encephalitogenic T cells. Here, we investigated the impact of Rai expression on astrocyte function both under basal conditions and in response to IL-17 treatment using a proteomic approach. We found that astrocytes and astrocyte-derived extracellular vesicles contain a set of proteins, to which Rai contributes, that are involved in the regulation of oligodendrocyte differentiation and myelination, nitrogen metabolism, and oxidative stress. The HIF-1α pathway and cellular energetic metabolism were the most statistically relevant molecular pathways and were related to ENOA and HSP70 dysregulation.https://www.mdpi.com/1422-0067/22/15/7933astrocytesmolecular adaptorIL-17proteomicsextracellular vesiclesHIF-1α |
| spellingShingle | Tommaso Montecchi Enxhi Shaba Domiziana De Tommaso Fabrizio Di Giuseppe Stefania Angelucci Luca Bini Claudia Landi Cosima Tatiana Baldari Cristina Ulivieri Differential Proteomic Analysis of Astrocytes and Astrocytes-Derived Extracellular Vesicles from Control and Rai Knockout Mice: Insights into the Mechanisms of Neuroprotection International Journal of Molecular Sciences astrocytes molecular adaptor IL-17 proteomics extracellular vesicles HIF-1α |
| title | Differential Proteomic Analysis of Astrocytes and Astrocytes-Derived Extracellular Vesicles from Control and Rai Knockout Mice: Insights into the Mechanisms of Neuroprotection |
| title_full | Differential Proteomic Analysis of Astrocytes and Astrocytes-Derived Extracellular Vesicles from Control and Rai Knockout Mice: Insights into the Mechanisms of Neuroprotection |
| title_fullStr | Differential Proteomic Analysis of Astrocytes and Astrocytes-Derived Extracellular Vesicles from Control and Rai Knockout Mice: Insights into the Mechanisms of Neuroprotection |
| title_full_unstemmed | Differential Proteomic Analysis of Astrocytes and Astrocytes-Derived Extracellular Vesicles from Control and Rai Knockout Mice: Insights into the Mechanisms of Neuroprotection |
| title_short | Differential Proteomic Analysis of Astrocytes and Astrocytes-Derived Extracellular Vesicles from Control and Rai Knockout Mice: Insights into the Mechanisms of Neuroprotection |
| title_sort | differential proteomic analysis of astrocytes and astrocytes derived extracellular vesicles from control and rai knockout mice insights into the mechanisms of neuroprotection |
| topic | astrocytes molecular adaptor IL-17 proteomics extracellular vesicles HIF-1α |
| url | https://www.mdpi.com/1422-0067/22/15/7933 |
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