ID | 61478 |
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Author |
Hiramatsu-Asano, Sumie
Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Sunahori-Watanabe, Katsue
Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Zeggar, Sonia
Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Katsuyama, Eri
Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Mukai, Tomoyuki
Department of Rheumatology, Kawasaki Medical School
Morita, Yoshitaka
Department of Rheumatology, Kawasaki Medical School
Wada, Jun
Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
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Abstract | Objective: The micro RNAs (miRNAs) and their target mRNAs are differentially expressed in various immune-mediated cells. Here, we investigated the role of Mir223 and sphingosine-1-phosphate receptor 1 (S1pr1) in the pathogenesis of systemic lupus erythematosus.
Methods: We analyzed miRNA and mRNA profiling data of CD4+ splenic T cells derived from MRL/MpJ-Faslpr/J mice. We performed 3′ untranslated region (UTR) luciferase reporter gene assay using human umbilical vein endothelial cells (HUVECs). We generated the B6-Mir223−/−Faslpr/lpr mice and the lupus phenotypes were analyzed.
Results: In CD4+ splenic T cells, we identified upregulation of miR-223-3p and downregulation of the possible target, S1pr1 by RNA sequencing of MRL/MpJ-Faslpr/J mice. The transfection with miR-223-3p mimic significantly suppressed a luciferase activity in HUVEC treated with a Lentivirus vector containing 3′ UTR of S1pr1. The mRNA levels of S1pr1 were significantly decreased after miR-223-3p overexpression. In B6-Mir223−/−Faslpr/lpr mice, the proportion of CD3+ T cells, CD3+CD4-CD8− cells, B cells, plasma cells, and S1PR1+CD4+ T cells in the spleen was significantly increased compared with that in B6-Mir223+/+Faslpr/lpr mice by flow cytometry. B6-Mir223−/−Faslpr/lpr mice demonstrated the elevation of glomerular and renal vascular scores associated with enhanced intraglomerular infiltration of S1PR1+CD4+ T cells.
Conclusion: Unexpectedly, the deletion of Mir223 exacerbated the lupus phenotypes associated with increased population of S1PR1+CD4+ T in spleen and the enhanced infiltration of S1PR1+CD4+ T cells in inflamed kidney tissues, suggesting compensatory role of Mir223 in the pathogenesis of lupus nephritis.
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Keywords | miR-223-3p
S1pr1
S1PR1(+)CD4(+) T cells
lupus nephritis
MRL/MpJ-Faslpr/J mice
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Published Date | 2021-01-26
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Publication Title |
Frontiers in Immunology
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Volume | volume11
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Publisher | Frontiers Media
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Start Page | 616141
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ISSN | 1664-3224
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Content Type |
Journal Article
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language |
English
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OAI-PMH Set |
岡山大学
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Copyright Holders | © 2021 Hiramatsu-Asano, Sunahori-Watanabe, Zeggar, Katsuyama, Mukai, Morita and Wada.
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File Version | publisher
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DOI | |
Web of Science KeyUT | |
Related Url | isVersionOf https://doi.org/10.3389/fimmu.2020.616141
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License | https://creativecommons.org/licenses/by/4.0/
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Funder Name |
Japan Society for the Promotion of Science
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助成番号 | 16K09895
16K09896
16K19601
16K19602
16K19600
17K09976
18K16151
20K17442
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