2022 Fiscal Year Final Research Report
Role of transcription factor Fli-1 in chemokine expression and SLE pathogenesis for development of novel therapies
Project/Area Number |
20K08804
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 54020:Connective tissue disease and allergy-related
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Research Institution | Fukushima Medical University |
Principal Investigator |
Shuzo Sato 福島県立医科大学, 医学部, 准教授 (20535231)
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Co-Investigator(Kenkyū-buntansha) |
鬼澤 道夫 福島県立医科大学, 医学部, 助教 (30783352)
渡辺 浩志 福島県立医科大学, 医学部, 教授 (40336467)
右田 清志 福島県立医科大学, 医学部, 教授 (60264214)
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Project Period (FY) |
2020-04-01 – 2023-03-31
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Keywords | ループス腎炎 / Fli-1 / ケモカイン / CXCL13 / ループスモデルマウス / SLE / 転写因子 |
Outline of Final Research Achievements |
Previous reports have shown that transcription factor Fli-1 regulates cytokine/chemokine expression in lupus nephritis. This study aims to elucidate association between Fli-1 and CXCL13 expression, a chemokine which attracts B cells and promotes ectopic lymphoid structures (TLS). Adult Fli-1+/- (heterozygote) MRL/lpr mice showed reduced serum CXCL13 levels and reduced mRNA expression of CXCL13 and Sox4 in the kidney compared to wild-type (WT) littermates. The CXCL13-positive and CXCR5-positive immune cells were also reduced in Fli-1+/- mice. Immunofluorescence microscopy showed reduced CXCL13/CD11b double positive cells, indicates reduced CXCL13 positive monocytes infiltration in TLS lesion of the kidney. Taken together, Fli-1 affects CXCL13 and Sox4 expression in the kidney, which may influence the severity of lupus-like nephritis in MRL/lpr mice. Fli-1 inhibition could be a novel target for treating lupus nephritis and SLE.
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Free Research Field |
リウマチ膠原病内科
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Academic Significance and Societal Importance of the Research Achievements |
ループス腎炎は全身性エリテマトーデス(SLE) に合併する最も頻度の高い臓器病変であり、SLEの予後を左右する重要な因子であるにも関わらず、未だ難治例の克服が問題となっている。転写因子Fli-1はサイトカイン、ケモカイン発現制御によってループス腎炎における炎症に関与しており、今回の研究でFli-1がCXCL13やSox4発現にも重要な役割を果たすことが判明した。Fli-1をはじめとした転写因子を制御することにより、すなわちドラッグリポジショニングや新規薬剤などの開発によりSLE治療へのさらなる貢献が期待できる。
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