Pathological involvement of RAGE/HMGB1 Axis in systemic lupus erythematosus

• Project/Area Number: 16K19600
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Collagenous pathology/Allergology
• Research Institution: Okayama University
• Principal Investigator: Watanabe Haruki 岡山大学, 大学病院, 助教 (10761132)
• Research Collaborator: WATANABE katsue ; SADA ken-ei ; YAMAMOTO hiroshi ; WADA jun
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: SLE / RAGE / プリスタン / 全身性エリテマトーデス / 肺血管炎 / 免疫学

Outline of Final Research Achievements

Intraperitoneal administration of pristane causes inflammation and symptoms similar to systemic lupus erythematosus (SLE) such as nephritis and arthritis. When pristane is administered to RAGE deficient C57BL/6 mouse, the survival rate tends to be improved as compared to wild-type mouse. Macrophages seem to rescue the survival. Furthermore, deletion of the RAGE gene in MRL/lpr mice, another spontaneous SLE model, reduced proteinuria and decreased the weight of spleen and lymph nodes, indicating that RAGE might be a therapeutic target for SLE.

Academic Significance and Societal Importance of the Research Achievements

RAGEのSLEにおける役割については、RAGEを阻害するsRAGEを別のSLEモデルマウスに投与するとSLEが改善したという報告と、別のSLEモデルマウスのRAGE遺伝子を欠損させるとSLEが悪化したという相反する報告がなされていた。本研究による2つのモデルマウスの検討からRAGEはSLEの有望な治療標的となる可能性が示された。

Research Products

• [Journal Article] Anti-high Mobility Group Box 1 Antibody Ameliorates Albuminuria in MRL/lpr Lupus-Prone Mice. (2017)
  • Author(s): Watanabe H, Watanabe KS, Liu K, Hiramatsu S, Zeggar S, Katsuyama E, Tatebe N, Akahoshi A, Takenaka F, Hanada T, Akehi M, Sasaki T, Sada KE, Matsuura E, Nishibori M, Wada J.
  • Journal Title: Mol Ther Methods Clin Dev Volume: 6 Pages: 31-39
  • DOI: 10.1016/j.omtm.2017.05.006
  • Peer Reviewed / Open Access