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Study of the Sialic Acid Modification and Kdn Accumulation in Acquired Cystic Kidney Disease

Research Project

Project/Area Number 19K17730
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 53040:Nephrology-related
Research InstitutionUniversity of Tsukuba

Principal Investigator

Kawanishi Kunio  筑波大学, 医学医療系, 助教 (00578750)

Project Period (FY) 2019-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2022: ¥260,000 (Direct Cost: ¥200,000、Indirect Cost: ¥60,000)
Fiscal Year 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords後天性嚢胞腎 / 後天性嚢胞腎随伴腎細胞癌 / シアル酸 / Kdn / バイオマーカー / 透析腎癌 / 後天性嚢胞腎随伴性腎細胞癌 / 糖鎖バイオマーカー / 血液透析 / 糖鎖解析 / ACD-RCC / ACKD / レクチンアレイ / RNAseq / 低真空走査型電子顕微鏡 / 後天性嚢胞腎 (ACKD) / 腎細胞癌
Outline of Research at the Start

透析患者では腎細胞癌の罹患率が非透析例の約15倍に上昇する。また、透析年数が進むにつれて、非遺伝性嚢胞疾患である後天性嚢胞腎を母地とする特殊な腎癌の頻度が増加する。透析腎癌は嚢胞に合併しやすく、今日の発達した画像検査技術を適応しても術前診断が困難な症例が多い。後天性嚢胞腎や透析腎癌の発症メカニズムの解明と、診断を補助する画期的な技術の開発(腫瘍マーカー)が必要である。本研究では、透析腎癌の癌組織、非癌部組織の遺伝子変動、糖鎖修飾を網羅的に解析し、特異的な糖鎖構造と、そのキャリアタンパクを同定する。腎不全モデルマウスの解析と合わせて、透析腎癌の発生メカニズムの解明と新規腫瘍マーカー開発を目指す。

Outline of Final Research Achievements

Acquired cystic kidney disease (ACKD), a non-hereditary cystic disease, occurs in kidneys of choronic kidney disease (CKD) patients. The frequency of renal cell carcinoma is 5- to 15-fold higher in hemodialysis patients than in non-hemodialysis patients, and the frequency of acquired cystic kidney-associated renal cell carcinoma (ACD-RCC) is known to increase with the number of years of dialysis. Accoding to the discoveries of deaminoneuraminic acid (Kdn) accumulation in hemodialysis patients, and the presence of anti-Kdn antibodies in human serum, we hypothesized that Kdn is involved in the development of ACKD and ACD-RCC. We established a method to detect Kdn-conjugated glycopeptides in patient tissues and cell cultures. Although we could not find Kdn-conjugated glycopeptides in ACD-RCC tissues, we found several unique sialylated peptides that could be usuful biomarkers for ACD-RCC.

Academic Significance and Societal Importance of the Research Achievements

透析患者のKdn蓄積とヒト血清中に抗Kdn抗体が存在するという発見から、ACKDのACD-RCCへの進展メカニズム解明を目指し、Kdn探索を行った。研究を通して、ACD-RCC組織からKdn型ペプチドを発見することはできなかったが、ヒト細胞株上でKdn型ペプチドを検出する手法を確立できた意義は大きい。また、研究期間中に米国での事前検討を深化させ、脊椎動物が保存するマンノース代謝経路とKdn産生の意義は過剰なマンノースの緩衝機構にあるとする学説を論文化できた。また研究の過程で透析腎癌マーカーとして有力な分子を複数発見し特許出願した社会的意義は大きく、検証のための多施設共同研究を開始できている。

Report

(5 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (19 results)

All 2023 2022 2021 2020 Other

All Journal Article (7 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 5 results,  Open Access: 4 results) Presentation (9 results) (of which Int'l Joint Research: 3 results,  Invited: 3 results) Remarks (2 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Exploring comprehensive glycan profiles of acquired cystic kidney disease associated renal cell carcinoma to establish a new diagnostic biomarker2021

    • Author(s)
      Kawanishi Kunio
    • Journal Title

      Impact

      Volume: 2021 Issue: 6 Pages: 40-42

    • DOI

      10.21820/23987073.2021.6.40

    • Related Report
      2021 Research-status Report
  • [Journal Article] Polyvinyl alcohol scaffolds and supplementation support 3D and sphere culturing of human cancer cell lines by reducing apoptosis and promoting cellular proliferation2021

    • Author(s)
      Okita Yukari、Zheng Ling、Kawanishi Kunio、Miyoshi Hirotoshi、Yanagihara Kazuyoshi、Kato Mitsuyasu
    • Journal Title

      Genes to Cells

      Volume: 26(5) Issue: 5 Pages: 336-343

    • DOI

      10.1111/gtc.12843

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Genetic Background and Clinicopathologic Features of Adult-onset Nephronophthisis2021

    • Author(s)
      Fujimaru Takuya、Kawanishi Kunio、et al.
    • Journal Title

      Kidney International Reports

      Volume: 未定 Issue: 5 Pages: 1346-1354

    • DOI

      10.1016/j.ekir.2021.02.005

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Evolutionary conservation of human ketodeoxynonulosonic acid production is independent of sialoglycan biosynthesis2021

    • Author(s)
      Kawanishi Kunio、Saha Sudeshna、Diaz Sandra、Vaill Michael、Sasmal Aniruddha、Siddiqui Shoib S.、Choudhury Biswa、Sharma Kumar、Chen Xi、Schoenhofen Ian C.、Sato Chihiro、Kitajima Ken、Freeze Hudson H.、M?nster-K?hnel Anja、Varki Ajit
    • Journal Title

      Journal of Clinical Investigation

      Volume: 131 Issue: 5

    • DOI

      10.1172/jci137681

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Exploring the Impact of Ketodeoxynonulosonic Acid in Host-Pathogen Interactions Using Uptake and Surface Display by Nontypeable Haemophilus influenzae2021

    • Author(s)
      Saha Sudeshna、Coady Alison、Sasmal Aniruddha、Kawanishi Kunio、Choudhury Biswa、Yu Hai、Sorensen Ricardo U.、Inostroza Jaime、Schoenhofen Ian C.、Chen Xi、M?nster-K?hnel Anja、Sato Chihiro、Kitajima Ken、Ram Sanjay、Nizet Victor、Varki Ajit
    • Journal Title

      mBio

      Volume: 12 Issue: 1

    • DOI

      10.1128/mbio.03226-20

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 後天性嚢胞腎随伴性腎細胞癌における糖鎖関連遺伝子の次世代シーケンサー解析2020

    • Author(s)
      川西 邦夫, 岡谷 千晶, 長田 道夫
    • Journal Title

      日本透析医会雑誌

      Volume: 35 Pages: 673-678

    • Related Report
      2020 Research-status Report
  • [Journal Article] Bidirectional, non-necrotizing glomerular crescents are the critical pathology in X-linked Alport syndrome mouse model harboring nonsense mutation of human COL4A52020

    • Author(s)
      Song Jiang Ying、Saga Nobuyuki、Kawanishi Kunio、Hashikami Kentaro、Takeyama Michiyasu、Nagata Michio
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 18891-18891

    • DOI

      10.1038/s41598-020-76068-4

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Identification of sialic acid-containing molecules to establish a new sialoglyco-biomarker for acquired cystic disease associated renal cell carcinoma (ACD-RCC)2022

    • Author(s)
      Kunio Kawanishi, Chiaki Nagai-Okatani, Shinichiro Fujita, Hiroaki Sakaue, Takashi Sato, Hiroaki Kaji, Masafumi Muratani, Mitsuyasu Kato, Atsushi Kuno
    • Organizer
      Sialoglyco2022
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 川西邦夫, 岡谷千晶, 佐藤隆, 坂上弘明, 久野敦, 加藤光保,2022

    • Author(s)
      腎臓・病理・糖鎖の3医学を結集したオミクス解析による癌・希少疾患のバイオマーカー開発プラットフォーム
    • Organizer
      第39回分子病理学研究会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Glycopathological Profiling of Acquired Cystic Disease Associated Renal Cell Carcinoma2021

    • Author(s)
      Kunio Kawanishi
    • Organizer
      1st East Asia Renal Pathology Conference
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] シアル酸生物学からみた後天性嚢胞腎随伴性腎細胞癌の新規バイオマーカー開発2021

    • Author(s)
      川西 邦夫
    • Organizer
      第11回分子腎臓フォーラム
    • Related Report
      2021 Research-status Report
  • [Presentation] 後天性嚢胞腎随伴性腎細胞癌における糖鎖遺伝子と糖鎖発現の網羅的解析2021

    • Author(s)
      川西 邦夫、岡谷 千晶、藤田 晋一郎、村谷 匡史、佐藤 隆、梶 裕之、久野 敦
    • Organizer
      第110回日本病理学会総会
    • Related Report
      2021 Research-status Report
  • [Presentation] Glycan profile of acquired cystic disease associated renal cell carcinoma using lectin microarray systems2020

    • Author(s)
      Kunio Kawanishi
    • Organizer
      the 63th Annual Meeting of the Japanese Society of Nephrology
    • Related Report
      2020 Research-status Report
  • [Presentation] シンポジウム10「透析腎癌」糖鎖解析からみえた透析腎癌の特徴2020

    • Author(s)
      川西 邦夫
    • Organizer
      第50回日本腎臓学会東部学術大会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] Glycopathological Profiling of Acquired Cystic Disease Associated Renal Cell Carcinoma2020

    • Author(s)
      Kunio Kawanishi
    • Organizer
      East Asia Renal Pathology Conference (International Travel Award 採択>COVID-19により延期)
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] シンポジウム「透析腎癌」透析腎癌の糖鎖解析2020

    • Author(s)
      川西邦夫
    • Organizer
      第50回日本腎臓学会東部学術大会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Remarks] 透析腎癌に特異的な糖鎖組織マーカーの確立を めざした臨床病理学的検討

    • URL

      https://www.tia-nano.jp/data/doc/1594268406_doc_61_0.pdf

    • Related Report
      2022 Annual Research Report
  • [Remarks] 体内のマンノース濃度を保つ仕組みを解明~進化の過程で選択された糖代謝経路~

    • URL

      https://www.tsukuba.ac.jp/journal/medicine-health/20210210140000.html

    • Related Report
      2020 Research-status Report
  • [Patent(Industrial Property Rights)] 腎細胞癌検出用糖タンパク質マーカー2023

    • Inventor(s)
      川西邦夫・久野敦・岡谷千晶・佐藤隆・坂上弘明・梶 裕之
    • Industrial Property Rights Holder
      川西邦夫・久野敦・岡谷千晶・佐藤隆・坂上弘明・梶 裕之
    • Industrial Property Rights Type
      特許
    • Filing Date
      2023
    • Related Report
      2022 Annual Research Report

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Published: 2019-04-18   Modified: 2024-12-25  

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