Potential role of RhoA GTPase regulation in type interferon signaling in systemic lupus erythematosus
© 2024. The Author(s)..
OBJECTIVE: Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by abnormal activation of the type I interferon (IFN) pathway, which results in tissue inflammation and organ damage. We explored the role of the RhoA GTPase in the type I IFN activation pathway to provide a potential basis for targeting GTPase signaling for the treatment of SLE.
METHODS: Total RNA was extracted from peripheral blood mononuclear cells (PBMCs) of SLE patients and healthy controls, and the mRNA expression levels of RhoA and IFN-stimulated genes were measured by SYBR Green quantitative reverse transcriptase-polymerase chain reaction. IFN-a-stimulated response element (ISRE)-luciferase reporter gene assays and Western blotting were conducted to assess the biologic function of RhoA. An enzyme-linked immunoassay (ELISA) measured C-X-C motif chemokine ligand 10 (CXCL10) protein expression.
RESULTS: Our studies demonstrate that the expression of RhoA in the PBMCs of SLE subjects was significantly higher than in healthy controls and positively correlated with type I IFN scores and type I IFN-stimulated gene (ISGs) expression levels. SiRNA-mediated knockdown of RhoA and the RhoA/ROCK inhibitor Y27632 reduced the activity of the type I IFN-induced ISRE, the signal transducer and activator of transcription 1 (STAT-1) phosphorylation, and the expression of CXCL10 and 2'-5'-oligoadenylate synthetase 1 (OAS1). Finally, we verified that Y27632 could significantly down-regulate the OAS1 and CXCL10 expression levels in the PBMCs of SLE patients.
CONCLUSION: Our study shows that RhoA positively regulates the activation of the type I IFN response pathway. Reducing the expression level of RhoA inhibits the abnormal activation of the type I IFN system, and the RhoA/ROCK inhibitor Y27632 decreases aberrant type I IFN signaling in SLE PBMCs, suggesting the possibility of targeting the RhoA GTPase for the treatment of SLE.
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:26 |
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| Enthalten in: |
Arthritis research & therapy - 26(2024), 1 vom: 20. Jan., Seite 31 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Fan, Wei [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 22.01.2024 Date Revised 12.03.2024 published: Electronic UpdateOf: Res Sq. 2023 Sep 20;:. - PMID 37790522 Citation Status MEDLINE |
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| doi: |
10.1186/s13075-024-03263-3 |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 0 | |a Potential role of RhoA GTPase regulation in type interferon signaling in systemic lupus erythematosus |
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| 500 | |a Date Revised 12.03.2024 | ||
| 500 | |a published: Electronic | ||
| 500 | |a UpdateOf: Res Sq. 2023 Sep 20;:. - PMID 37790522 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2024. The Author(s). | ||
| 520 | |a OBJECTIVE: Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by abnormal activation of the type I interferon (IFN) pathway, which results in tissue inflammation and organ damage. We explored the role of the RhoA GTPase in the type I IFN activation pathway to provide a potential basis for targeting GTPase signaling for the treatment of SLE | ||
| 520 | |a METHODS: Total RNA was extracted from peripheral blood mononuclear cells (PBMCs) of SLE patients and healthy controls, and the mRNA expression levels of RhoA and IFN-stimulated genes were measured by SYBR Green quantitative reverse transcriptase-polymerase chain reaction. IFN-a-stimulated response element (ISRE)-luciferase reporter gene assays and Western blotting were conducted to assess the biologic function of RhoA. An enzyme-linked immunoassay (ELISA) measured C-X-C motif chemokine ligand 10 (CXCL10) protein expression | ||
| 520 | |a RESULTS: Our studies demonstrate that the expression of RhoA in the PBMCs of SLE subjects was significantly higher than in healthy controls and positively correlated with type I IFN scores and type I IFN-stimulated gene (ISGs) expression levels. SiRNA-mediated knockdown of RhoA and the RhoA/ROCK inhibitor Y27632 reduced the activity of the type I IFN-induced ISRE, the signal transducer and activator of transcription 1 (STAT-1) phosphorylation, and the expression of CXCL10 and 2'-5'-oligoadenylate synthetase 1 (OAS1). Finally, we verified that Y27632 could significantly down-regulate the OAS1 and CXCL10 expression levels in the PBMCs of SLE patients | ||
| 520 | |a CONCLUSION: Our study shows that RhoA positively regulates the activation of the type I IFN response pathway. Reducing the expression level of RhoA inhibits the abnormal activation of the type I IFN system, and the RhoA/ROCK inhibitor Y27632 decreases aberrant type I IFN signaling in SLE PBMCs, suggesting the possibility of targeting the RhoA GTPase for the treatment of SLE | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Autoimmunity | |
| 650 | 4 | |a RhoA | |
| 650 | 4 | |a RhoA/ROCK inhibitor | |
| 650 | 4 | |a Systemic lupus erythematosus | |
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| 650 | 7 | |a Interferon Type I |2 NLM | |
| 650 | 7 | |a Amides |2 NLM | |
| 650 | 7 | |a Pyridines |2 NLM | |
| 700 | 1 | |a Wei, Bo |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Xuyan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Yi |e verfasserin |4 aut | |
| 700 | 1 | |a Xiao, Pingping |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Kaiyan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Yi Qin |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Jinmei |e verfasserin |4 aut | |
| 700 | 1 | |a Leng, Lin |e verfasserin |4 aut | |
| 700 | 1 | |a Bucala, Richard |e verfasserin |4 aut | |
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