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Significance of glycan abnormalities in diabetic nephropathy

Research Project

Project/Area Number 19H03675
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 53040:Nephrology-related
Research InstitutionOkayama University

Principal Investigator

Wada Jun  岡山大学, 医歯薬学域, 教授 (30294408)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000)
Fiscal Year 2021: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2019: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
Keywords糖尿病性腎症 / 尿レクチンアレイ / 網羅的糖鎖プロファイル / C型レクチン受容体 / 糖鎖合成酵素 / 糖鎖異常 / O型糖鎖 / レクチンアレイ / 糖鎖プロファイル
Outline of Research at the Start

2型糖尿病患者のコホート研究で、尿レクチンアレイ解析による糖鎖の網羅的解析を施行したところ、尿中レクチン(SNA, ABA, Jacalin, ACA, RCA120)への結合シグナルの上昇が腎機能低下のリスクであることを見出した。これらのレクチンが認識する糖鎖は糖タンパク質上のT-antigenやsialyl-Tnで、いずれも合成不全糖鎖で癌組織において発現する抗原でもある。尿中糖鎖の糖尿病性腎症のバイオマーカーとして重要性と腎症進展のメカニズムに関与を示し、糖尿病性腎症の新規治療ターゲットとしての意義を明らかにする。

Outline of Final Research Achievements

Urinary lectin array analysis was successfully developed by using 45 lectins with different glycan binding specificity. In the cohort of patients with type 2 diabetes (n=680), higher glycan binding signals to SNA, ABA, Jacalin, ACA, and RCA120 predicted the 30% eGFR decline after 4 years follow-up. The lectin histochemistry demonstrated that T-antigen, Tn-antigen, sialyl-T, sialyl-Tn, and Core 3 recognized by these lectins were localized proximal tubular cells and secreted to the urine.

Academic Significance and Societal Importance of the Research Achievements

糖尿病性腎症において近位尿細管細胞に発現するTn-antigenやsialyl-Tnと、マクロファージ上に存在しそれらの糖鎖構造を認識するC型レクチン受容体の相互作用が進展に関与している可能性を示した。今後の糖尿病性腎症の診断や治療の開発への研究の展開が期待される。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • Research Products

    (28 results)

All 2022 2021 2020 2019

All Journal Article (26 results) (of which Int'l Joint Research: 11 results,  Peer Reviewed: 26 results,  Open Access: 21 results) Presentation (2 results) (of which Int'l Joint Research: 1 results,  Invited: 2 results)

  • [Journal Article] Development of Urinary Diagnostic Biomarker for IgA Nephropathy by Lectin Microarray.2022

    • Author(s)
      Onishi Y, Mise K, Kawakita C, Uchida HA, Sugiyama H, Sugawara R, Yamaguchi S, Yoshida M, Mitsuhashi T, Yamada M, Hirabayashi J, Wada J.
    • Journal Title

      Am J Nephrol.

      Volume: 53 Issue: 1 Pages: 10-20

    • DOI

      10.1159/000520998

    • NAID

      120007190701

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Adipocyte-Specific Inhibition of Mir221/222 Ameliorates Diet-Induced Obesity Through Targeting Ddit4.2022

    • Author(s)
      Yamaguchi S, Zhang D, Katayama A, Kurooka N, Sugawara R, Albuayjan HHH, Nakatsuka A, Eguchi J, Wada J.
    • Journal Title

      Front Endocrinol (Lausanne).

      Volume: 12 Pages: 750261-750261

    • DOI

      10.3389/fendo.2021.750261

    • NAID

      120007188342

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Circulating GPIHBP1 levels and microvascular complications in patients with type 2 diabetes: A cross-sectional study.2022

    • Author(s)
      Kurooka N, Eguchi J, Murakami K, Kamei S, Kikutsuji T, Sasaki S, Seki A, Yamaguchi S, Nojima I, Watanabe M, Higuchi C, Katayama A, Uchida HA, Nakatsuka A, Shikata K, Wada J.
    • Journal Title

      J Clin Lipidol.

      Volume: 22 Issue: 2 Pages: 21-26

    • DOI

      10.1016/j.jacl.2022.01.006

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Novel Urinary Glycan Biomarkers Predict Cardiovascular Events in Patients With Type 2 Diabetes: A Multicenter Prospective Study With 5-Year Follow Up (U-CARE Study 2).2021

    • Author(s)
      Mise K, Imamura M, Yamaguchi S, Watanabe M, Higuchi C, Katayama A, Miyamoto S, Uchida HA, Nakatsuka A, Eguchi J, Hida K, Nakato T, Tone A, Teshigawara S, Matsuoka T, Kamei S, Murakami K, Shimizu I, Miyashita K, Ando S, Nunoue T, Yoshida M, Yamada M, Shikata K, Wada J.
    • Journal Title

      Front Cardiovasc Med.

      Volume: 8 Pages: 668059-668059

    • DOI

      10.3389/fcvm.2021.668059

    • NAID

      120007053373

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Upregulation of Mir342 in Diet-Induced Obesity Mouse and the Hypothalamic Appetite Control.2021

    • Author(s)
      Zhang D, Yamaguchi S, Zhang X, Yang B, Kurooka N, Sugawara R, Albuayjan HHH, Nakatsuka A, Eguchi J, Hiyama TY, Kamiya A, Wada J.
    • Journal Title

      Front Endocrinol (Lausanne).

      Volume: 12 Pages: 727915-727915

    • DOI

      10.3389/fendo.2021.727915

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Kidney outcomes associated with SGLT2 inhibitors versus other glucose-lowering drugs in real-world clinical practice: the japan chronic kidney disease database2021

    • Author(s)
      Nagasu H, Yano Y, Kanegae H, Heerspink HJL, Tamura K, et al.
    • Journal Title

      Diabetes Care.

      Volume: 44 Issue: 11 Pages: 2542

    • DOI

      10.2337/dc21-1081

    • URL

      https://pure.teikyo.jp/en/publications/eabd49ea-a511-42c8-a1da-79b540e01738

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Deletion of Mir223 Exacerbates Lupus Nephritis by Targeting S1pr1 in Faslpr/lpr Mice2021

    • Author(s)
      Hiramatsu-Asano Sumie、Sunahori-Watanabe Katsue、Zeggar Sonia、Katsuyama Eri、Mukai Tomoyuki、Morita Yoshitaka、Wada Jun
    • Journal Title

      Frontiers in Immunology

      Volume: 11 Pages: 616141-616141

    • DOI

      10.3389/fimmu.2020.616141

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Novel urinary glycan profiling by lectin array serves as the biomarkers for predicting renal prognosis in patients with IgA nephropathy2021

    • Author(s)
      Kawakita Chieko、Mise Koki、Onishi Yasuhiro、Sugiyama Hitoshi、Yoshida Michihiro、Yamada Masao、Wada Jun
    • Journal Title

      Scientific Reports

      Volume: 11(1) Issue: 1 Pages: 3394-3394

    • DOI

      10.1038/s41598-020-77736-1

    • NAID

      120007144312

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Lgals9 deficiency ameliorates obesity by modulating redox state of PRDX2.2021

    • Author(s)
      Nunoue T, Yamaguchi S, Teshigawara S, Katayama A, Nakatsuka A, Eguchi J, Niki T, Wada J.
    • Journal Title

      Sci Rep.

      Volume: 16 Issue: 1 Pages: 5991-5991

    • DOI

      10.1038/s41598-021-85080-1

    • NAID

      120007004155

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A Vaspin-HSPA1L complex protects proximal tubular cells from organelle stress in diabetic kidney disease2021

    • Author(s)
      Nakatsuka A, Yamaguchi S, Eguchi J, Kakuta S, Iwakura Y, Sugiyama H, Wada J.
    • Journal Title

      Commun Biol .

      Volume: 4 Issue: 1 Pages: 373-373

    • DOI

      10.1038/s42003-021-01902-y

    • NAID

      120007004153

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Adult kidney stem/progenitor cells contribute to regeneration through the secretion of trophic factors2020

    • Author(s)
      Tsuji Kenji、Kitamura Shinji、Sang Yizhen、Fukushima Kazuhiko、Wada Jun
    • Journal Title

      Stem Cell Research

      Volume: 46 Pages: 101865-101865

    • DOI

      10.1016/j.scr.2020.101865

    • NAID

      120006887353

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Association of explanatory histological findings and urinary protein and serum creatinine levels at renal biopsy in lupus nephritis: a cross-sectional study2020

    • Author(s)
      Katsuyama Eri、Miyawaki Yoshia、Sada Ken-ei、Asano Yosuke、Hayashi Keigo、Yamamura Yuriko、Hiramatsu-Asano Sumie、Morishita Michiko、Ohashi Keiji、Watanabe Haruki、Katsuyama Takayuki、Narazaki Mariko、Matsumoto Yoshinori、Wada Jun
    • Journal Title

      BMC Nephrology

      Volume: 21(1) Issue: 1 Pages: 208-208

    • DOI

      10.1186/s12882-020-01868-9

    • NAID

      120006862797

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sodium Glucose Co-Transporter 2 Inhibitor Ameliorates Autophagic Flux Impairment on Renal Proximal Tubular Cells in Obesity Mice2020

    • Author(s)
      Fukushima Kazuhiko、Kitamura Shinji、Tsuji Kenji、Sang Yizhen、Wada Jun
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 21(11) Issue: 11 Pages: 4054-4054

    • DOI

      10.3390/ijms21114054

    • NAID

      120006869600

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Semaphorin3A-Inhibitor Ameliorates Doxorubicin-Induced Podocyte Injury2020

    • Author(s)
      Sang Yizhen、Tsuji Kenji、Inoue-Torii Akiko、Fukushima Kazuhiko、Kitamura Shinji、Wada Jun
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 21(11) Issue: 11 Pages: 4099-4099

    • DOI

      10.3390/ijms21114099

    • NAID

      120006869601

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Protective Effect of Chlorogenic Acid on Vascular Senescence via the Nrf2/HO-1 Pathway2020

    • Author(s)
      Hada Yoshiko、Uchida Haruhito A.、Otaka Nozomu、Onishi Yasuhiro、Okamoto Shugo、Nishiwaki Mariko、Takemoto Rika、Takeuchi Hidemi、Wada Jun
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 21(12) Issue: 12 Pages: 4527-4527

    • DOI

      10.3390/ijms21124527

    • NAID

      120006877909

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Genetic Deletion of Vasohibin-2 Exacerbates Ischemia-Reperfusion-Induced Acute Kidney Injury2020

    • Author(s)
      Miyake Hiromasa、Tanabe Katsuyuki、Tanimura Satoshi、Nakashima Yuri、Morioka Tomoyo、Masuda Kana、Sugiyama Hitoshi、Sato Yasufumi、Wada Jun
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 21 Issue: 12 Pages: 4545-4545

    • DOI

      10.3390/ijms21124545

    • NAID

      120006872424

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Deep Learning Could Diagnose Diabetic Nephropathy with Renal Pathological Immunofluorescent Images2020

    • Author(s)
      Kitamura Shinji、Takahashi Kensaku、Sang Yizhen、Fukushima Kazuhiko、Tsuji Kenji、Wada Jun
    • Journal Title

      Diagnostics

      Volume: 10(7) Issue: 7 Pages: 466-466

    • DOI

      10.3390/diagnostics10070466

    • NAID

      120006880205

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Dysfunction of CD8 + PD-1 + T cells in type 2 diabetes caused by the impairment of metabolism-immune axis2020

    • Author(s)
      Nojima I, Eikawa S, Tomonobu N, Hada Y, Kajitani N, Teshigawara S, Miyamoto S, Tone A, Uchida HA, Nakatsuka A, Eguchi J, Shikata K, Udono H, Wada J.
    • Journal Title

      Sci Rep.

      Volume: 10 Issue: 1 Pages: 14928-14928

    • DOI

      10.1038/s41598-020-71946-3

    • NAID

      120006891215

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Dynamin 1 is important for microtubule organisation and stabilisation in glomerular podocytes2020

    • Author(s)
      The Mon La , Tachibana, H., Li, S.A., Abe, T., Seiriki, S., Nagaoka, H., Takashima, E., Takeda, T., Ogawa, D., Makino, S., Asanuma, K., Watanabe, M., Tian, X., Ishibe, S., Sakane, A., Sasaki, T., Wada, J., Takei, K., Yamada, H.
    • Journal Title

      FASEB Journal

      Volume: 34 Issue: 12 Pages: 16449-16463

    • DOI

      10.1096/fj.202001240rr

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Inhibition of Interleukin-6 Signaling Attenuates Aortitis, Left Ventricular Hypertrophy and Arthritis in Interleukin-1 Receptor Antagonist Deficient Mice.2020

    • Author(s)
      Yoshiko Hada, Haruhito A. Uchida, Tomoyuki Mukai, Fumiaki Kojima, Masashi Yoshida, Hidemi Takeuchi, Yuki Kakio, Nozomu Otaka,Yoshitaka Morita, Jun Wada.
    • Journal Title

      Clin. Sci. (Lond).

      Volume: 134 Issue: 20 Pages: 2771-2787

    • DOI

      10.1042/cs20201036

    • NAID

      120007168219

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Risk of higher dose methotrexate for renal impairment in patients with rheumatoid arthritis2020

    • Author(s)
      Hayashi Keigo、Sada Ken-Ei、Asano Yosuke、Asano Sumie Hiramatsu、Yamamura Yuriko、Ohashi Keiji、Morishita Michiko、Watanabe Haruki、Narazaki Mariko、Matsumoto Yoshinori、Wada Jun
    • Journal Title

      Scientific Reports

      Volume: 10(1) Issue: 1 Pages: 18715-18715

    • DOI

      10.1038/s41598-020-75655-9

    • NAID

      120006939591

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Vasohibin-2 Aggravates Development of Ascending Aortic Aneurysms But Not Abdominal Aortic Aneurysms Nor Atherosclerosis in ApoE Deficient Mice2020

    • Author(s)
      Otaka Nozomu、Uchida Haruhito A、Okuyama Michihiro、Hada Yoshiko、Onishi Yasuhiro、Kakio Yuki、Takeuchi Hidemi、Umebayashi Ryoko、Tanabe Katsuyuki、Subramanian Venkateswaran、Daugherty Alan、Sato Yasufumi、Wada Jun
    • Journal Title

      American Journal of Hypertension

      Volume: in press Issue: 5 Pages: 467-475

    • DOI

      10.1093/ajh/hpaa181

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Podocyte autophagy is associated with foot process effacement and proteinuria in patients with minimal change nephrotic syndrome.2020

    • Author(s)
      Ogawa-Akiyama A, Sugiyama H, Kitagawa M, Tanaka K, Kano Y, Mise K, Otaka N, Tanabe K, Morinaga H, Kinomura M, Uchida HA, Wada J.
    • Journal Title

      PLoS One.

      Volume: 15(1) Issue: 1 Pages: 1-15

    • DOI

      10.1371/journal.pone.0228337

    • NAID

      120006862788

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Inhibitory Effects of Tofogliflozin on Cardiac Hypertrophy in Dahl Salt-Sensitive and Salt-Resistant Rats Fed a High-Fat Diet2019

    • Author(s)
      Kimura T, Nakamura K, Miyoshi T, Yoshida M, Akazawa K, Saito Y, Akagi S, Ohno Y, Kondo M, Miura D, Wada J, Ito H.
    • Journal Title

      International Heart Journal

      Volume: 60 Issue: 3 Pages: 728-735

    • DOI

      10.1536/ihj.18-392

    • NAID

      130007655762

    • ISSN
      1349-2365, 1349-3299
    • Year and Date
      2019-05-30
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Gut microbiome-derived phenyl sulfate contributes to albuminuria in diabetic kidney disease2019

    • Author(s)
      Kikuchi Koichi、Saigusa Daisuke、Kanemitsu Yoshitomi、Matsumoto Yotaro、Tsukamoto Hiroki、Abe Takaaki
    • Journal Title

      Nature Communications

      Volume: 10 Issue: 1 Pages: 1835-1835

    • DOI

      10.1038/s41467-019-09735-4

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Renal tubular injury exacerbated by Vasohibin-1 deficiency in a murine cisplatin-induced acute kidney injury model.2019

    • Author(s)
      Tanimura S, Tanabe K, Miyake H, Masuda K, Tsushida K, Morioka T, Sugiyama H, Sato Y, Wada J.
    • Journal Title

      Am J Physiol Renal Physiol.

      Volume: 317(2)

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] We’re good! We fang it! Debate about SGLT2 inhibitors in DKD. Con (less aggressive/less universal use).2019

    • Author(s)
      Wada J
    • Organizer
      WCN 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 挑戦する生活習慣病の生化学-次世代の治療戦略を目指して-生活習慣病における糖鎖とレクチン2019

    • Author(s)
      和田淳
    • Organizer
      第92回日本生化学学会大会
    • Related Report
      2019 Annual Research Report
    • Invited

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Published: 2019-04-18   Modified: 2023-01-30  

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