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Elucidation of the pathogenic mechanism of diabetic nephropathy by oral microorganism-derived blood TLR ligand and development for prevention

Research Project

Project/Area Number 15H05060
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Social dentistry
Research InstitutionOkayama University (2017)
Fukuoka Dental College (2015-2016)

Principal Investigator

SAWA YOSHIHIKO  岡山大学, 医歯薬学総合研究科, 教授 (70271666)

Co-Investigator(Kenkyū-buntansha) 加藤 幸成  東北大学, 医学系研究科, 教授 (00571811)
畠山 雄次  福岡歯科大学, 口腔歯学部, 教授 (40302161)
坂上 竜資  福岡歯科大学, 口腔歯学部, 教授 (50215612)
福島 秀文  東北大学, 歯学研究科(研究院), 准教授 (70412624)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2017: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2016: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2015: ¥11,050,000 (Direct Cost: ¥8,500,000、Indirect Cost: ¥2,550,000)
Keywords歯周病 / 糖尿病性腎症 / toll-like receptor / Porphyromonas gingivalis / 糸球体硬化 / lipopolysaccharide / 歯周疾患 / 歯学 / 終末糖化産物 / 糸球体内皮細胞 / TGF-β / I型コラーゲン / 糖尿病マウス / 口腔微生物 / P. gingivalis / 1型コラーゲン
Outline of Final Research Achievements

Diabetes is known to increase the possibility of becoming nephropathy when it comes to periodontitis, but the mechanism is not known. In an experiment using diabetic mice, we found that blood vessels of a urine generating device, called glomeruli of the kidney, express 'toll-like receptors' that recognize bacterial components when it comes to diabetes. We also found that injection of periodontal disease pathogen into mucosa of diabetic mouse oral cavity causes nephropathy. It is thought that germs of periodontal disease enter the blood vessels of the oral cavity, go around the body, enter the kidney and bind to the receptor and cause nephropathy. In periodontitis, bacteria easily enter the blood vessel with tooth brushing. For people with diabetes, prevention of periodontitis is considered to prevent the diabetic nephropathy.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • Research Products

    (18 results)

All 2018 2017 2016 Other

All Int'l Joint Research (2 results) Journal Article (9 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 9 results,  Open Access: 9 results,  Acknowledgement Compliant: 1 results) Presentation (7 results) (of which Int'l Joint Research: 6 results)

  • [Int'l Joint Research] Richard Peters Darveau/Department of Periodontics/University of Washington(米国)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] Thao T. To/Department of Periodontics/University of Washington(米国)

    • Related Report
      2016 Annual Research Report
  • [Journal Article] LpMab-23-recognizing cancer-type podoplanin is a novel predictor for a poor prognosis of early stage tongue cancer.2018

    • Author(s)
      Miyazaki, A., Nakai, H., Sonoda, T., Kaneko, M.K., Kato, Y., Sawa, Y., Hiratsuka, H.
    • Journal Title

      Oncotarget

      Volume: 9 Issue: 30 Pages: 21156-21165

    • DOI

      10.18632/oncotarget.24986

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Expression and Dynamics of Podoplanin in Cultured Osteoblasts with Mechanostress and Mineralization Stimulus2018

    • Author(s)
      Takenawa, T., Kanai, T., Kitamura, T., Yoshimura, Y., Sawa, Y., Iida, J.
    • Journal Title

      ACTA HISTOCHEMICA ET CYTOCHEMICA

      Volume: 51 Issue: 1 Pages: 41-52

    • DOI

      10.1267/ahc.17031

    • NAID

      130006405040

    • ISSN
      0044-5991, 1347-5800
    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The promotion of nephropathy by Porphyromonas gingivalis lipopolysaccharide via toll-like receptors.2017

    • Author(s)
      Kajiwara, K., Takata, S., To, T., Takara, K., Hatakeyama, Y., Tamaoki, S., Darveau, R.P., Ishikawa, H., Sawa, Y.
    • Journal Title

      Diabetology & Metabolic Syndrome

      Volume: 9 Issue: 1 Pages: 73-73

    • DOI

      10.1186/s13098-017-0271-8

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Morphological study of tooth development in podoplanin-deficient mice.2017

    • Author(s)
      Takara, K., Maruo, N., Oka, K., Kaji, C., Hatakeyama, Y., Sawa, N., Kato, Y., Sawa, Y.
    • Journal Title

      PLoS One

      Volume: 12 Issue: 2 Pages: e0171912-e0171912

    • DOI

      10.1371/journal.pone.0171912

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effects of a Chemically Synthesized Leucine-Rich Amelogenin Peptide (csLRAP) on Chondrogenic and Osteogenic Cells2017

    • Author(s)
      Matsuda, Y., Hatakeyama, Y., Nakashima, K., Kamogashira, N., Hatakeyama, J., Sawa, Y.
    • Journal Title

      Journal of Hard Tissue Biology

      Volume: 26 Issue: 1 Pages: 51-60

    • DOI

      10.2485/jhtb.26.51

    • NAID

      130005188392

    • ISSN
      1341-7649, 1880-828X
    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Distinct Role of Transforming Growth Factor-Beta 1 and Fibroblast Growth Factors in Human Amelobastoma Epithelial Cell Proliferation2017

    • Author(s)
      Matsuda Y, Kamogashira N, Hatakeyama Y, Mikami T, Nakashima K, Hatakeyama J, Tamaoki S, Sawa Y, Ishikawa H
    • Journal Title

      Biochemistry and Molecular Biology

      Volume: 2(1) Issue: 1 Pages: 1-5

    • DOI

      10.11648/j.bmb.20170201.11

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Effects of TLR4 blocking on diabetic nephropathy promoted by the Porphyromonas gingivalis lipopolysaccharide.2017

    • Author(s)
      Kajiwara, K., Takata S., To, T., Takara, K., Hatakeyama, Y., Tamaoki, S., Darveau, R., Ishikawa, I., Sawa, Y.
    • Journal Title

      Diabetology & Metabolic Syndrome

      Volume: 印刷中

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Differentiation of Apical Bud Cells in a Newly Developed Apical Bud Transplantation Model Using GFP Transgenic Mice as Donor.2016

    • Author(s)
      Maruo N, Sakagami R, Yoshinaga Y, Okamura K, Sawa Y.
    • Journal Title

      PLoS One

      Volume: 11(3)

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Novel Monoclonal Antibody LpMab-17 Developed by CasMab Technology Distinguishes Human Podoplanin from Monkey Podoplanin.2016

    • Author(s)
      Kato Y, Ogasawara S, Oki H, Honma R, Takagi M, Fujii Y, Nakamura T, Saidoh N, Kanno H, Umetsu M, Kamata S, Kubo H, Yamada M, Sawa Y, Morita K, Harada H, Suzuki H, Kaneko MK.
    • Journal Title

      Monoclon Antib Immunodiagn Immunother

      Volume: 35(2) Pages: 109-116

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Effects of TLR4 blocking on diabetic nephropathy promoted by the Porphyromon as gingivalis lipopolysaccharide2017

    • Author(s)
      梶原、高田、藤田、高良、畠山、玉置、石川、沢
    • Organizer
      第65回国際歯科研究学会日本部会(JADR)学術大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] The morphological investigation of head and neck organs in the systemic podoplanin knockout mice2016

    • Author(s)
      Kaji C, Takara K, Hatakeyama Y, Kojima H, Sawa Y.
    • Organizer
      International Association of Dental research
    • Place of Presentation
      Seoul
    • Year and Date
      2016-06-22
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Porphyromonas gingivalis lipopolysaccharide promote diabetic nephropathy through TLR22016

    • Author(s)
      Kajiwara K, Takata S, Hatakeyama Y, Ishikawa H, Sawa Y.
    • Organizer
      International Association of Dental research
    • Place of Presentation
      Seoul
    • Year and Date
      2016-06-22
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The expression of podoplanin and bone-associated proteins in the osteoblasts and craniofacial osteocytes with mechanical stress2016

    • Author(s)
      Kanai K, Sawa Y.
    • Organizer
      International Association of Dental research
    • Place of Presentation
      Seoul
    • Year and Date
      2016-06-22
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Study for the apical bud differentiation model using green mice2016

    • Author(s)
      Maruo N, Sakagami R, Yoshinaga Y, Sawa Y.
    • Organizer
      International Association of Dental research
    • Place of Presentation
      Seoul
    • Year and Date
      2016-06-22
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The distribution of podoplanin in the tooth and craniofacial bone2016

    • Author(s)
      Takara K, Kaji C, Hatakeyama Y, Kojima H, Sawa Y.
    • Organizer
      International Association of Dental research
    • Place of Presentation
      Seoul
    • Year and Date
      2016-06-22
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The cytokine inductions in glomerular endothelial cells with Porphyromonas gingivalis lipopolysaccharide through TLR22016

    • Author(s)
      Takata S, Kajiwara K, Hatakeyama Y, Ishikawa H, Sawa Y.
    • Organizer
      International Association of Dental research
    • Place of Presentation
      Seoul
    • Year and Date
      2016-06-22
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research

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Published: 2015-04-16   Modified: 2022-10-14  

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