Anti-podocyte antibodies determination and its mechanisms of podocyte injury

• Project/Area Number: 24790852
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Kidney internal medicine
• Research Institution: Yokohama City University
• Principal Investigator: NAGAHAMA Kiyotaka 横浜市立大学, 医学部, 助教 (00336538)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 糸球体上皮細胞 / ループス腎炎 / 自己抗体 / ネフリン / SLE / 糸球体腎炎 / Integrin

Research Abstract

Surface protein of mouse podocytes was purified and subjected to immunoblotting. The nitrocellulose membranes were incubated with IgG purified from SLE model mice or its control mice. IgG from the model mice, not the control mice, reacted with 110-kD molecule of podocyte surface proteins, then the band was excised to mass spectrometry analysis. Based on molecules revealed by MASS spectrometry and the molecular size, we identified that integrin beta 1 would be a candidate molecule for an autoantigen on podocytes of SLE model mice. Recombinant mouse integrin beta 1 was then generated. Immunoblotting using this recombinant ITGB1 revealed anti-ITGB1 antibody specifically in the SLE model mice. ELISA was also performed to reveal that the antibody started to elevate at two weeks after spleen cell transfer then peaked at 4 weeks. These data strongly suggest that anti-integrin beta 1 antibodies are generated and deposit on the podocytes in the SLE model mice.

Research Products

• [Journal Article] Rituximab treatment for adult purpura nephritis with nephrotic syndrome (2013)
  • Author(s): Ishiguro H, Hashimoto T, Akata M, Suzuki S, Azushima K, Kobayashi Y, Kanaoka T, Yoshida S, Wakui H, Oshikawa J, Nagahama K, Inayama Y, Tamura K, Toya Y, Umemura S
  • Journal Title: Intern Med Volume: 52(10) Pages: 1079-83
  • NAID: 130003365604
  • URL: https://www.jstage.jst.go.jp/article/internalmedicine/52/10/52_52.9325/_articl
  • Peer Reviewed
• [Journal Article] A case of synchronous mucinous metaplasia and neoplasia of the female genital tract without an STK11 or KRAS mutation (2013)
  • Author(s): Nagahama K, Yamanaka S, Nakayama T, Tokinaga A, Asai-Sato M, Miyagi E, Tanaka R, Furuya M
  • Journal Title: Gynecol Oncol Case Rep . Ne Volume: 5 Pages: 4-5
  • URL: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3862322/
  • Peer Reviewed
• [Journal Article] Relapsing proliferative glomerulonephritis with monoclonal IgG deposits showing circumferential crescentic glomerulonephritis (2013)
  • Author(s): Oshio M, Fujii T, Kusaura T, Nagahama K
  • Journal Title: Clinical Kidney Journal Volume: 6(6) Pages: 635-8
  • URL: http://ckj.oxfordjournals.org/content/6/6/635.full?sid=3808ae2b-ee19-4a7e-a783-3d971c41f495
  • Peer Reviewed
• [Journal Article] Enhanced Ang receptor-associated protein in renal tubule suppresses Ang-dependent hypertension (2013)
  • Author(s): Wakui H, Tamura K, Masuda S, Tsurumi-Ikeya Y, Fujita M, Maeda A, Ohsawa M, Azushima K, Uneda K, Matsuda M, Kitamura K, Uchida S, Toya Y, Kobori H, Nagahama K, Yamashita A, Umemura S.
  • Journal Title: Hypertension Volume: 61(6) Pages: 1203-10
  • DOI: 10.1161/hypertensionaha.111.00572
  • Peer Reviewed / Open Access
• [Journal Article] Biopsy-proven drug-induced tubulointerstitial nephritis in a patient with acute kidney injury and alcoholic severe acute pancreatitis (2013)
  • Author(s): Yoshioka, W. Mori, T. Nagahama, K. Tamura, T.
  • Journal Title: BMJ Case Rep Volume: 3 Pages: 1-4
  • DOI: 10.1136/bcr-2013-008557
  • Peer Reviewed
• [Journal Article] Rituximab treatment for adult purpura nephritis with nephrotic syndrome (2013)
  • Author(s): Ishiguro, H. Hashimoto, T. Akata, M. Suzuki, S. Azushima, K. Kobayashi, Y. Kanaoka, T. Yoshida, S. Wakui, H. Oshikawa, J. Nagahama, K. Inayama, Y. Tamura, K. Toya, Y. Umemura, S.
  • Journal Title: Internal Medicine Volume: 52 Pages: 1079-1083
  • NAID: 130003365604
  • Peer Reviewed
• [Journal Article] A case of synchronous mucinous metaplasia and neoplasia of the female genital tract without an STK11 or KRAS mutation (2013)
  • Author(s): Nagahama K, Yamanaka S, Nakayama T, Tokinaga A, Asai-Sato M, Miyagi E, Tanaka R, Furuya M
  • Journal Title: Gynecol Oncol Case Rep. Volume: vol 5 Pages: 4-5
  • DOI: 10.1016/j.gynor.2013.02.005
  • Peer Reviewed
• [Journal Article] Relapsing proliferative glomerulonephritis with monoclonal IgG deposits showing circumferential crescentic glomerulonephritis (2013)
  • Author(s): Oshio, M. Fujii, T. Kusaura, T. Nagahama, K.
  • Journal Title: Clinical Kidney Journal Volume: 6 Pages: 635-638
  • DOI: 10.1093/ckj/sft121
  • Peer Reviewed
• [Journal Article] Identification of miR-30d as a novel prognostic maker of prostate cancer (2012)
  • Author(s): Furuya Mitsuko
  • Journal Title: Oncotarget Volume: 36 Pages: 589-600
  • DOI: 10.1097/pas.0b013e3182475240
  • Peer Reviewed
• [Journal Article] Impaired CXCL4 expression in tumor-associated macrophages (TAMs) of ovarian cancers arising in endometriosis (2012)
  • Author(s): Furuya M, Tanaka R, Miyagi E, Kami D ,Nagahama K, Miyagi Y, Nagashima Y, Hirahara F, Inayama Y, Aoki I.
  • Journal Title: Cancer Biol Ther Volume: 13 Pages: 671-680
  • DOI: 10.4161/cbt.20084
  • Peer Reviewed
• [Journal Article] Warthin tumor arising from the minor salivary gland (2012)
  • Author(s): Iwai T, Baba J, Murata S, Mitsudo K, Maegawa J, Nagahama K, Tohnai I
  • Journal Title: J Craniofac Surg Volume: 23(5)
  • DOI: 10.1097/scs.0b013e318254359f
  • Peer Reviewed
• [Journal Article] Inducible colitis-associated glycome capable of stimulating the proliferation of memory CD4+ T cells (2012)
  • Author(s): Nishida A, Nagahama K, Imaeda H, Ogawa A, Lau CW, Kobayashi T, Hisamatsu T, Preffer FI, Mizoguchi E, Ikeuchi H, Hibi T, Fukuda M, Andoh A, Blumberg RS, Mizoguchi A.
  • Journal Title: The Journal of Experimental Medicine Volume: 209(13) Pages: 2383-2394
  • DOI: 10.1084/jem.20112631
  • Peer Reviewed
• [Journal Article] Sunitinib-induced nephrotic syndrome and irreversible renal dysfunction (2012)
  • Author(s): Takahashi D, Nagahama K, Tsuura Y, Tanaka H, Tamura T
  • Journal Title: Clinical and Experimental Nephrology Volume: 16(2) Pages: 310-315
  • DOI: 10.1007/s10157-011-0543-9
  • NAID: 10030739069
  • Peer Reviewed
• [Presentation] SLEモデルマウスにはintegrin β1に対する自己抗体が存在する (2013)
  • Author(s): 長濱清隆,古屋充子,山中正二,長嶋洋治,青木一郎
  • Organizer: 第56回日本腎臓学会総会
  • Place of Presentation: 東京国際フォーラム、東京
  • Year and Date: 2013-05-12
• [Presentation] MRSA感染を契機に発症しネフローゼを呈した Henoch-Schonlein紫斑病に対しシクロスポリンが奏功した1例 (2012)
  • Author(s): 萬代新太郎,安藝昇太,稲葉直人,青柳誠,田中啓之,長濱清隆,津浦幸夫,田村禎一
  • Organizer: 第42回日本腎臓学会東部学術集会
  • Place of Presentation: 朱鷺メッセ、新潟
  • Year and Date: 2012-10-14
• [Presentation] 全身性エリテマトーデスの経過中に急性腎不全を発症しHUS/TTPかCNI腎症の鑑別が困難であった1例 (2012)
  • Author(s): 長濱清隆
  • Organizer: 第55回日本腎臓学会総会
  • Place of Presentation: パシフィコ横浜、横浜
  • Year and Date: 2012-06-02
• [Presentation] Synchronous and multifocal mucinous lesions involving the femalegenitaltractの一例 (2012)
  • Author(s): 長濱清隆,中山崇,山中正二,古屋充子
  • Organizer: 第101回日本病理学会総会
  • Place of Presentation: 京王プラザ、東京
  • Year and Date: 2012-04-28
• [Presentation] SLEモデルマウスにはintegrin β1に対する自己抗体が存在する
  • Author(s): 長濱清隆, 古屋充子, 山中正二, 長嶋洋治, 青木一郎.
  • Organizer: 第56回日本腎臓学会総会
  • Place of Presentation: 東京国際フォーラム（東京都千代田区）
• [Presentation] 腎生検病理診断コンサルテーション・アンド・レビュー
  • Author(s): 長濱 清隆
  • Organizer: 第55回日本腎臓学会総会
  • Place of Presentation: パシフィコ横浜(神奈川県）
  • Invited
• [Presentation] Synchronous and multifocal mucinous lesions involving the female genital tractの一例
  • Author(s): 長濱 清隆
  • Organizer: 第101回日本病理学会総会
  • Place of Presentation: 京王プラザホテル（東京都）
• [Presentation] MRSA感染を契機に発症しネフローゼを呈したHenoch-Schonlein紫斑病に対しシクロスポリンが奏功した１例
  • Author(s): 萬代 新太郎
  • Organizer: 第42回日本腎臓学会東部学術集会
  • Place of Presentation: 朱鷺メッセ(新潟県）
• [Book] 臨床腎臓内科学 (2013)
  • Author(s): 長濱清隆, 他
  • Publisher: 南山堂
• [Book] 臨床腎臓内科学 (2013)
  • Author(s): 長濱 清隆
  • Publisher: 南山堂