MicroRNA profiling of human lupus nephritis and murine lupus-like nephritis.

• Project/Area Number: 19591167
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: 膠原病・アレルギー・感染症内科学
• Research Institution: Kobe University
• Principal Investigator: KAWANO Seiji Kobe University, 医学部附属病院, 講師 (20351512)
• Co-Investigator(Kenkyū-buntansha): KUMAGAI Shunichi 神戸大学, 大学院医学研究科, 教授 (00153346) ; NAKAMACHI Yuji 神戸大学, 医学部付属病院, 臨床検査技師 (80379429)
• Co-Investigator(Renkei-kenkyūsha): HONJO Tasuku 京都大学, 医学研究科, 客員教授 (80090504) ; MINATO Nagahiro 京都大学, 医学研究科, 教授 (40137716) ; TANAKA Yoshimasa 京都大学, 医学研究科, 特定准教授 (90280700) ; OKAZAKI Taku 徳島大学, 疾患ゲノム研究センター, 教授 (00362468) ; MORINOBU Akio 神戸大学, 大学院医学研究科, 准教授 (10294216) ; HATACHI Saori (財)田附興風会医学研究所, 第4研究部, 研究員 (70414117)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2007: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 膠原病学 / ループス腎炎 / PD-1 / トレランス / マイクロRNA / NZB / W F1 / ループス賢炎

Research Abstract

NZB/W F1マウスに抗PD-1抗体と抗PD-L1抗体の投与実験を行い、前者はCD4+PD-1+T細胞を減らして腎炎を改善し、後者は逆にCD4+PD-1+T細胞が蓄積し腎炎を悪化させた。CD4+PD-1+T細胞はIFN-γ高産生細胞であり、腎炎病態への積極的関与が強く示唆された。また同マウスの抗PD-L1抗体投与後に、脾臓から単離したCD4+PD-1+T細胞とCD4+PD-1-T細胞よりmiRNAおよびmRNAを抽出し、比較プロファイリングを行ってCD4+PD-1+T細胞に特異的なmiRNAおよびmRNAの同定を試みた。

Research Products

• [Journal Article] miR-124a is a key regulator of proliferation and MCP1 secretion in fibroblast like synoviocytes from patients with rheumatoid arthritis (2009)
  • Author(s): Nakamachi Y, Kawano S, Takenokuchi M,Nishimura K, Sakai Y, Chin T, Saura R, Kurosaka M, and Kumagai S
  • Journal Title: Arthritis & Rheumatism 60(5) Pages: 1294-1304
  • Peer Reviewed
• [Journal Article] MicroRNA-124a Is a Key Regulator of Proliferation and Monocyte Chemoattractant Protein 1 Secretion in Fibroblast-like Synoviocytes From Patients With Rheumatoid Arthritis (2009)
  • Author(s): Nakamachi Y, et al
  • Journal Title: Arthritis & Rheumatism 61(印刷中)
  • Peer Reviewed
• [Journal Article] DR negativity is a distinctive feature of M1/M2 AML cases with NPM1 mutation (2008)
  • Author(s): Syampurnawati M, Tatsumi E, Ardianto B, Takenokuchi M, Nakamachi Y, Kawano S, Kumagai S, Saigo K, Matsui T, Takahashi T, Nagai K, Gunadi h, Nishio H, Yabe H, Kondo S, Hayashi Y.
  • Journal Title: Leukemia Res 32(7) Pages: 1141-3
  • Peer Reviewed
• [Journal Article] Prevalence of disease-specific antinuclear antibodies in general population: Estimates from annual physical examinations of residents of a small town over a five-year period (2008)
  • Author(s): Hayashi N, Koshiba M, Nishimura K, Sugiyama D, Nakamura T, Morinobu S, Kawano S, and Kumagai S
  • Journal Title: Modern Rheumatol 18(2) Pages: 153-60
  • Peer Reviewed
• [Journal Article] Prevalence of disease-specific antinuclear antibodies in general population : estimates from annual physical examinations of residents of a small town over a 5-year period. (2008)
  • Author(s): Hayashi N, et al.
  • Journal Title: Mod Rheumatol. 18 Pages: 153-60
  • Peer Reviewed
• [Journal Article] DR negativity is a distinctive feature of M1/M2 AML cases with NPM1 mutation. (2008)
  • Author(s): Syampumawati M, et al
  • Journal Title: Leuk Res. 32 Pages: 1141-3
  • Peer Reviewed
• [Journal Article] Dissociation of rheumatoid factor level from that of international reference material due to wrong calibrator in Dade Behring kit (2007)
  • Author(s): Hayashi N, Kawano S, Sugiyama D, Nishimura K, Nakazawa T, Morinobu A, and Kumagai S
  • Journal Title: Modern Rheumatol 17 Pages: 447-49
  • Peer Reviewed
• [Journal Article] Thioredoxin may exert a protective effect against tissue damage caused by oxidative stress in the salivary glands of patients with Sjogren's syndrome (2007)
  • Author(s): Kurimoto C, Kawano S, Tsuji G, Hatachi S, Jikimoto T, Sugiyama D, Kasagi S, Komori T, Nakamura H, Yodoi J, and Kumagai S
  • Journal Title: Thioredoxin may exert a protective effect against tissue damage caused by oxidative stress in the salivary glands of patients with Sjogren's syndrome 34 Pages: 2035-43
  • Peer Reviewed
• [Journal Article] Kamae I, and Kumagai S. Meta-analysis: diagnostic accuracy of anti-cyclic citrullinated peptide antibody and rheumatoid factor for rheumatoid arthritis (2007)
  • Author(s): Nishimura K, Sugiyama D, Kogata Y, Tsuji G, Nakazawa T, Kawano S, Saigo K, Morinobu A, Koshiba M, Kuntz KM, Kamae I, and Kumagai S. Meta-analysis
  • Journal Title: Ann Intern Med 146 Pages: 797-808
  • Peer Reviewed
• [Journal Article] Is SS-A/Ro52 a hydrogen peroxide-sensitive signaling molecule? (2007)
  • Author(s): Nobuhara Y, Kawano S, Kageyama G, Sugiyama D, Saegusa J, and Kumagai S
  • Journal Title: Antioxidants & Redox Signaling 9 Pages: 385-91
  • Peer Reviewed
• [Journal Article] HLA-DR-negative AML (M1 and M2): FLT3 mutations (ITD and D835) and cell-surface antigen expression (2007)
  • Author(s): Syampurnawati M, Tatsumi E, Furuta K, Takenokuchi M, Nakamachi Y, Kawano S, Kumagai S, Saigo K, Matsui T, Takahashi T, Nagai KI, Yabe H, Kondo S, and Hayashi Y
  • Journal Title: Leuk Res 31 Pages: 921-9
  • Peer Reviewed
• [Journal Article] Thioredoxin may exert a protective effect against tissue damage caused byoxidative stress in salivary glands of patients with Sjogren's syndrome. (2007)
  • Author(s): Kurimoto C, et. al.
  • Journal Title: J. Rheumatol. 34 Pages: 2035-43
  • Peer Reviewed
• [Journal Article] Meta-analysis: diagnostic accuracy of anti-cyclic citrullinated peptide antibody and rheumatoid factor for rheumatoid arthritis. (2007)
  • Author(s): Nishimura K, et. al.
  • Journal Title: Ann Intern Med. 146 Pages: 797-808
  • Peer Reviewed
• [Journal Article] Overestimation of serum levels of rheumatoid factor caused by the presence of an incorrect calibrator in the Dade Behring kit. (2007)
  • Author(s): Hayashi N, et. al.
  • Journal Title: Mod Rheumatol. 17 Pages: 447-9
  • Peer Reviewed
• [Journal Article] Quantitative Detection of PML-RAR RARα Fusion Transcript by Real-time PCR with A Single Primer Pair
  • Author(s): Takenokuchi M, Kawano S, Nakamachi Y, Yoneda K, Joho K, Saigo K, Tatsumi E, Kumagai S
  • Journal Title: J Clin Lab Anal. In press Pages: 0-0
  • Peer Reviewed
• [Presentation] (2008)
  • Author(s): Kasagi S, Kawano S, Morinobu A, Hatachi S, Okazaki T, Tanaka Y, Minato N, Honjo T, and Kumagai S
  • Organizer: Kasagi S, Kawano S, Morinobu A, Hatachi S, Okazaki T, Tanaka Y, Minato N, Honjo T, and Kumagai S
  • Place of Presentation: 京都
  • Year and Date: 2008-12-03
• [Presentation] Involvement of IFN-g producing CD4+PD-1+ T cells in lupus-prone NZB/W F1 mice (2008)
  • Author(s): Kasagi S, Kawano S, Morinobu A, Hatachi S, Simatani K, Tanaka Y, Minato N, Okazaki T, Honjo T, and Kumagai S
  • Organizer: American College of Rheumatology, Annual Scientific Meeting
  • Place of Presentation: at San Francisco
  • Year and Date: 2008-10-28
• [Presentation] Involvement of IFN-g producing CD4+PD・1+T cells in lupus-prone NZB/W F1 mice. (2008)
  • Author(s): Kasagi s, et al.
  • Organizer: 米国リウマチ学会年次集会
  • Place of Presentation: サンフランシスコ、USA
  • Year and Date: 2008-10-28
• [Presentation] ループス腎炎モデルマウスにおけるPD-1およびPD-L1の機能解析 (2008)
  • Author(s): 笠木伸平, 河野誠司、森信暁雄、籏智さおり、熊谷俊一
  • Organizer: 第52回日本リウマチ学会総会・学術集会
  • Place of Presentation: 札幌
  • Year and Date: 2008-04-21
• [Presentation] The role of PD-1/PD-L in the pathogenesis of nephritis of NZB/W F1 mice (2008)
  • Author(s): Kasagi S, Kawano S, Morinobu A, Tanaka Y, Okazaki T, Minato N, Honjo T, and Kumagai S
  • Organizer: 第11回京都免疫ワークショップ
  • Place of Presentation: 京都
  • Year and Date: 2008-03-22
• [Presentation] Expression of PD-1/PD-L1 in the development of lupus-like nephritis in NZB/W F1 mice (2007)
  • Author(s): Kasagi S, Kawano S, Morinobu A, Hatachi S, Tanaka Y, Okazaki T, Minato N, Honjo T, and Kumagai S
  • Organizer: 第37回日本免疫学会総会・学術集会
  • Place of Presentation: 東京
  • Year and Date: 2007-11-20
• [Presentation] Expression of PD-1/PD-L1 in the development of lupus-like nephritis in NZB/W mice. (2007)
  • Author(s): 笠木伸平、他
  • Organizer: 第37回日本免疫学会
  • Place of Presentation: 高輪プリンスホテル(東京)
  • Year and Date: 2007-11-20