Injuries of glomerular basement membrane in the progression of glomerular diseases

• Project/Area Number: 17K09717
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Nippon Medical School
• Principal Investigator: SHIMIZU AKIRA 日本医科大学, 大学院医学研究科, 大学院教授 (00256942)
• Co-Investigator(Kenkyū-buntansha): 石井 永一 日本医科大学, 大学院医学研究科, 研究生 (00193243) ; 康 徳東 日本医科大学, 医学(系)研究科(研究院), その他 (00571952)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 係蹄基底膜障害 / 糸球体疾患 / 糸球体上皮細胞 / IV型コラーゲンα鎖 / 低真空走査電子顕微鏡 / 電子顕微鏡 / 糸球体係蹄 / 腎生検病理診断 / IV型コラーゲンのα鎖 / 蛍光抗体法 / 菲薄基底膜病 / IV型コラーゲンのα3,4,5鎖 / 腎糸球体係蹄 / immune complex型糸球体腎炎 / 病理学 / 腎臓病学 / 糸球体腎炎 / 係蹄基底膜 / 尿中バイオマーカー

Outline of Final Research Achievements

We investigated qualitatively and ultrastructurally for the injury of glomerular basement membrane (GBM) and podocytes in several glomerular diseases. The qualitative alterations of the injured GBM were assessed by immunostaining of α1,1,2 and α3,4,5 of type IV collagen. The ultrastructural alterations of the injured GBM and podocytes were evaluated by the low-vacuum scanning electron microscope (LV-SEM) for light microscopic specimens with PAM, platinum-blue, or both staining. In the experimental and clinical glomerular diseases with hematuria, proteinuria, and/or renal dysfunctions, specific GBM and/or podocyte alterations were recognized qualitatively by immunostaining for α-chains of type IV collagen and ultrastructurally by LV-SEM. In the glomerular diseases, the specific GBM and/or podocyte alterations developed, and the qualitative and ultrastructural evaluation of these injury was useful for understanding the pathological condition of glomerular diseases.

Academic Significance and Societal Importance of the Research Achievements

低真空走査電顕(LV-SEM)は通常の透過型電子顕微鏡 (透過電顕)とは異なり、光学顕微鏡用の標本をそのまま高倍率の電顕的な観察が可能になるため、簡単な処置で短時間に広範囲に電顕的観察が可能である。LV-SEMの日常腎生検病理診断への応用の至適条件を設定した。また、糸球体係蹄基底膜障害における質的変化はIV型コラーゲンα鎖の蛍光抗体法の観察で、また障害係蹄基底膜の超微形態学的変化は LV-SEMにより広範囲に観察が可能であることを明らかにした。それぞれの糸球体疾患には特有の係蹄基底膜障害が進展しており、それらを明らかにすることは、疾患の病態の評価に役立つ。

Research Products

• [Journal Article] Renal Complications after Hematopoietic Stem Cell Transplantation: Role of Graft-Versus-Host Disease in Renal Thrombotic Microangiopathy (2020)
  • Author(s): Mii A, Shimizu A, Yamaguchi H, Tsuruoka S.
  • Journal Title: Journal of Nippon Medical School Volume: 87 Issue: 1 Pages: 7-12
  • DOI: 10.1272/jnms.JNMS.2020_87-102
  • NAID: 130007807465
  • ISSN: 1345-4676, 1347-3409
  • Year and Date: 2020-02-15
  • Peer Reviewed
• [Journal Article] Monoclonal Immunoglobulin Deposition Disease and Related Diseases (2019)
  • Author(s): Kanzaki G, Okabayashi Y, Nagahama K, Ohashi R, Tsuboi N, Yokoo T, Shimizu A.
  • Journal Title: Journal of Nippon Medical School Volume: 86 Issue: 1 Pages: 2-9
  • DOI: 10.1272/jnms.JNMS.2019_86-1
  • NAID: 130007620535
  • ISSN: 1345-4676, 1347-3409
  • Year and Date: 2019-01-15
  • Peer Reviewed
• [Journal Article] Group 1 innate lymphoid cells are involved in the progression of experimental anti-glomerular basement membrane glomerulonephritis and are regulated by peroxisome proliferator-activated receptor α. (2019)
  • Author(s): Okabayashi Y, Nagasaka S, Kanzaki G, Tsuboi N, Yokoo T, Shimizu A.
  • Journal Title: Kidney Int. Volume: Oct;96(4) Issue: 4 Pages: 942-956
  • DOI: 10.1016/j.kint.2019.04.039
  • Peer Reviewed
• [Journal Article] A case of membranous nephropathy diagnosed with lupus nephritis 11 years after onset. (2019)
  • Author(s): Yamada T, Itagaki F, Aratani S, Kawasaki S, Terada K, Mugishima K, Kashiwagi T, Shimizu A, Tsuruoka S.
  • Journal Title: CEN Case Rep Volume: 8 Issue: 4 Pages: 301-307
  • DOI: 10.1007/s13730-019-00412-5
  • Peer Reviewed
• [Journal Article] Bevacizumab-induced immunoglobulin A vasculitis with nephritis: A case report. (2019)
  • Author(s): Endo Y, Negishi K, Hirayama K, Suzuki H, Shimizu A.
  • Journal Title: Medicine (Baltimore) Volume: 98(45) Issue: 45 Pages: e17870-e17870
  • DOI: 10.1097/md.0000000000017870
  • Peer Reviewed
• [Journal Article] 糸球体疾患の免疫・病理 (2019)
  • Author(s): 岡林佑典, 清水章
  • Journal Title: 腎と透析 Volume: 86 Pages: 505-512
• [Journal Article] 病因診断における腎生検の役割 -腎疾患の病因を病理からどうアプローチするのか?- (2019)
  • Author(s): 三井亜希子, 清水章
  • Journal Title: 腎と透析 Volume: 87 Pages: 546-552
• [Journal Article] Pathologic glomerular characteristics and glomerular basement membrane alterations in biopsy-proven thin basement membrane nephropathy. (2019)
  • Author(s): Kajimoto Y, Endo Y, Terasaki M, Kunugi S, Igarashi T, Mii A, Terasaki Y, Shimizu A.
  • Journal Title: Clin Exp Nephrol. Volume: 23(5) Issue: 5 Pages: 638-649
  • DOI: 10.1007/s10157-018-01687-1
  • Peer Reviewed
• [Journal Article] Optimal conditions and the advantages of using laser microdissection and liquid chromatography tandem mass spectrometry for diagnosing renal amyloidosis (2018)
  • Author(s): Aoki Michiko、Kang Dedong、Katayama Akira、Kuwahara Naomi、Nagasaka Shinya、Endo Yoko、Terasaki Mika、Kunugi Shinobu、Terasaki Yasuhiro、Shimizu Akira
  • Journal Title: Clin Exp Nephrol Volume: 25 Issue: 4 Pages: 871-880
  • DOI: 10.1007/s10157-018-1533-y
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Radiation-induced premature cellular senescence involved in glomerular diseases in rats. (2018)
  • Author(s): Aratani S, Tagawa M, Nagasaka S, Sakai Y, Shimizu A, Tsuruoka S.
  • Journal Title: Sci Rep Volume: 8 Issue: 1 Pages: 16812-16812
  • DOI: 10.1038/s41598-018-34893-8
  • Peer Reviewed
• [Journal Article] Importance of frequency and morphological characteristics of nodular diabetic glomerulosclerosis in diabetic nephropathy. (2018)
  • Author(s): Yasuda F, Mii A, Morita M, Aoki M, Tagawa M, Aratani S, Kaneko T, Sakai Y, Shimizu A
  • Journal Title: Hum Pathol Volume: 75 Pages: 95-103
  • DOI: 10.1016/j.humpath.2018.01.019
  • Peer Reviewed
• [Journal Article] 軽・重鎖沈着症 (2018)
  • Author(s): 勝馬愛, 清水章
  • Journal Title: 腎と透析 Volume: 84 Pages: 533-538
• [Journal Article] Banff分類 (2018)
  • Author(s): 勝馬愛, 清水章
  • Journal Title: 腎と透析 Volume: 85 Pages: 499-506
• [Journal Article] 腎臓学この一年の進歩: 腎生検病理診断学の最近の進歩 (2018)
  • Author(s): 遠藤陽子, 清水章
  • Journal Title: 日本腎臓学会誌 Volume: 60 Pages: 28-35
• [Journal Article] 加齢に伴う腎臓の組織学的変化の特徴 (2017)
  • Author(s): 橘靖子, 湯村和子, 清水章
  • Journal Title: Geriatric Medicine（老年医学） Volume: 55 Pages: 1317-1321
• [Presentation] 抗糸球体基底膜腎炎ラットにおいてPPARαはCD8陽性細胞浸潤抑制を介して半月体形成を抑制する (2017)
  • Author(s): 岡林佑典, 永坂真也, 神崎剛, 荒谷紗絵, 田川雅子, 勝馬愛, 青木路子, 金光剛史, 梶本雄介, 康徳東, 長濱清隆, 清水章
  • Organizer: 日本腎臓学会学術総会（第60回）
• [Presentation] 液体クロマトグラフィタンデム型質量分析法によるアミロイド蛋白の同定 (2017)
  • Author(s): 青木路子, 康徳東, 桑原尚美, 新井孝司, 田川雅子, 勝馬愛, 荒谷紗絵, 梶本雄介, 岡林佑典, 永坂真也, 寺崎美佳, 清水章
  • Organizer: 日本病理学会(第106回)
• [Presentation] 糸球体腎炎におけるNETs形成に関わるシトルリン化ヒストンを有する好中球 (2017)
  • Author(s): 木村英人, 三井亜希子, 若松恭子, 鶴岡秀一, 清水章
  • Organizer: 日本腎臓学会学術総会（第60回）
• [Presentation] 菲薄基底膜病における糸球体係蹄障害と臨床病理学的検討 (2017)
  • Author(s): 梶本雄介, 田川雅子, 荒谷紗絵, 勝馬愛, 青木路子, 金光剛史, 岡林佑典, 永坂真也, 康徳東, 清水章
  • Organizer: 日本病理学会総会（第106回）
• [Book] IgA腎症の病態と治療(編 富野 康日己、川村 哲也、鈴木 祐介)・IgA腎症の病理 典型例から鑑別疾患まで (p159-169) (2019)
  • Author(s): 遠藤陽子, 清水章
  • Total Pages: 317
  • Publisher: 中外医学社
  • ISBN: 9784498224469
• [Book] AKI 急性腎障害 治療の実際: AKIの病理 (p41-49) (2018)
  • Author(s): 勝馬愛, 清水章
  • Total Pages: 262
  • Publisher: 日本医事新報社
  • ISBN: 9784784944873
• [Book] 腎生検病理アトラス 改訂版, (2017)
  • Author(s): 清水章
  • Publisher: 東京医学社