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Development of the novel therapeutic strategy for diabetic nephropathy through anti-inflammatory effects.

Research Project

Project/Area Number 21591031
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Kidney internal medicine
Research InstitutionOkayama University

Principal Investigator

SHIKATA Kenichi  岡山大学, 岡山大学病院, 教授 (00243452)

Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2009: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords腎臓病学 / 糖尿病性腎症 / microinflammation / osteopontin / cholecystokinin / 炎症 / 糖尿病 / マクロファージ / Cholecystokinin / Osteopontin
Research Abstract

We have demonstrated that low grade inflammation, microinflammation, is involved in the pathogenesis of diabetic nephropathy as well as of atherosclerosis. We have recently reported that anti-inflammatory agents such as statin and thiazolidinedione show renoprotective effects through anti-inflammatory actions in diabetic animals. In this study, 1) We induced diabetes into osteopontin knockout(KO) mice. Osteopontin KO mice showed the improvement of tissue injuries and inflammatory reactions in the kidney. 2) We found that GLP-1 receptor is expressed on monocte/macrophage and glomerular endothelial cells. GLP-1 receptor agonist showed renoprotective effects on diabetic rats through anti-inflammatory actions. These results suggest that osteopontin play a role in the pathogenesis of diabetic nephropathy and GLP-1 receptor agonist might be beneficial for the treatment of diabetic nephropathy.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (51 results)

All 2012 2011 2010 2009 Other

All Journal Article (32 results) (of which Peer Reviewed: 32 results) Presentation (15 results) Book (4 results)

  • [Journal Article] Cholecystokinin plays a novel protective role in diabetic kidney through anti-inflammatory actions on macrophage : anti-inflammatory effect of cholecystokinin2012

    • Author(s)
      Miyamoto S, Shikata K, Miyasaka K, Okada S, Sasaki M, Kodera R, Hirota D, Kajitani N, Takatsuka T, Kataoka HU, Nishishita S, Sato C, Funakoshi A, Nishimori H, Uchida HA, Ogawa D, Makino H
    • Journal Title

      Diabetes

      Volume: 61 Pages: 897-907

    • NAID

      40019575963

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] High glucose increases metallothionein expression in renal proximal tubular epithelial cells2012

    • Author(s)
      Ogawa D, Asanuma M, Miyazaki I, Tachibana H, Wada J, Sogawa N, Sugaya T, Kitamura S, Maeshima Y, Shikata K, Makino H
    • Journal Title

      Exp Diabetes Res

      Pages: 534872-534872

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Phenotypic change of macrophages in the progression of diabetic nephropathy ; sialoadhesin-positive activated macrophages are increased in diabetic kidney2012

    • Author(s)
      永瀬亮
    • Journal Title

      Clin Exp Nephrol

      Volume: (in press)

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cholecystokinin plays a novel protective role in diabetic kidney through anti-inflammatory actions on macrophage. -anti-inflammatory effect of CCK-2012

    • Author(s)
      宮本聡
    • Journal Title

      Diabetes

      Volume: (in press)

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Activation of peroxisome proliferator-activated receptor delta inhibits streptozotocin-induced diabetic nephropathy through anti-inflammatory mechanisms in mice2011

    • Author(s)
      Matsushita Y, Ogawa D, Wada J, Yamamoto N, Shikata K, Sato C, Tachibana H, Toyota N, Makino H
    • Journal Title

      Diabetes

      Volume: 60 Pages: 960-968

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Glucagon-like peptide-1 receptor agonist ameliorates renal injury through its anti-inflammatory action without lowering blood glucose level in a rat model of type 1 diabetes2011

    • Author(s)
      Kodera R, Shikata K, Kataoka HU, Takatsuka T, Miyamoto S, Sasaki M, Kajitani N, Nishishita S, Sarai K, Hirota D, Sato C, Ogawa D, Makino H
    • Journal Title

      Diabetologia

      Volume: 54 Pages: 965-978

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article]2011

    • Author(s)
      Sato C, Shikata K, Hirota D, Sasaki M, Nishishita S, Miyamoto S, Kodera R, Ogawa D, Tone A, Kataoka HU, Wada J, Kajitani N, Makino H
    • Journal Title

      Diabetes

      Volume: 60 Pages: 189-199

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Intercellular adhesion molecule-1 plays a critical role in glomerulosclerosis after subtotal nephrectomy2011

    • Author(s)
      Kido Y, Ogawa D, Shikata K, Sasaki M, Nagase R, Okada S, Usui Kataoka HU, Wada J, Makino H
    • Journal Title

      Clin Exp Nephrol

      Volume: 15 Pages: 212-219

    • NAID

      10029005164

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Renoprotective effects of clarithromycin via reduction of urinary MCP-1 levels in type 2 diabetic patients2011

    • Author(s)
      Tone A, Shikata K, Nakagawa K, Hashimoto M, Makino H
    • Journal Title

      Clin Exp Nephrol

      Volume: 15 Pages: 79-85

    • NAID

      10029004515

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Comparison of insulin detemir and insulin glargine on glycemic variability in patients with type 1 and type 2 diabetes2011

    • Author(s)
      Tone A, Iseda I, Higuchi C, Tsukamoto K, Katayama A, Matsushita Y, Hida K, Wada J, Shikata K
    • Journal Title

      Exp Clin Endocrinol Diabetes

      Volume: 118 Pages: 320-324

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] The Relation between estimated glomerular filtration rate(eGFR) and proteinuria in Okayama prefecture, Japan2011

    • Author(s)
      Miyatake N, Shikata K, Makino H, Numata T
    • Journal Title

      Environ Health Prev Med

      Volume: 16 Pages: 191-195

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Comparison of ventilatory threshold between subjects with and without proteinuria in Japanese2011

    • Author(s)
      Miyatake N, Shikata K, Makino H, Numata T
    • Journal Title

      Health

      Volume: 3 Pages: 394-399

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Decreasing serum uric acid levels might be associated with improving estimated glomerular filtration rate(eGFR) in Japanese men2011

    • Author(s)
      Miyatake N, Shikata K, Makno H, Numata T
    • Journal Title

      Health

      Volume: 3 Pages: 498-503

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] The relation between estimated glomerular filtration rate(eGFR) and coffee consumption in the Japanese2011

    • Author(s)
      Miyatake N, Shikata K, Makino H, Numata T
    • Journal Title

      Health

      Volume: 3 Pages: 549-552

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Comparison of muscle strength between subjects with and without proteinuria2011

    • Author(s)
      Miyatake N, Shikata K, Makino H, Numata T
    • Journal Title

      Health

      Volume: 3 Pages: 698-702

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] High glucose increases metallothionein expression in renal proximal tubular epithelial cells2011

    • Author(s)
      小川大輔
    • Journal Title

      Exp Diabetes Res

      Volume: 534,872

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Involvement of MAPKs in ICAM-1 expression in glomerular endothelial cells in diabetic nephropathy2011

    • Author(s)
      渡辺直美
    • Journal Title

      Acta Med Okayama

      Volume: 65 Pages: 247-257

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The macrophage is a key factor in renal injuries caused by glomerular hyperfiltration2011

    • Author(s)
      佐々木基史
    • Journal Title

      Acta Med Okayama

      Volume: 65 Pages: 81-89

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The relation between estimated glomerular filtration rate and proteinuria in Okayama Prefecture, Japan2011

    • Author(s)
      宮武伸行
    • Journal Title

      Environ Health Prev Med

      Volume: 16

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] P-selectin giycoprotein ligand-1 deficiency is protective against obesity-related insulin resistance2011

    • Author(s)
      佐藤千景
    • Journal Title

      Diabetes

      Volume: 60 Pages: 189-199

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Activation of peroxisome proliferator-activated receptor delta inhibits streptozotocin-induced diabetic nephropathy through anti-inflammatory mechanisms in mice.2011

    • Author(s)
      Matsushita Y, Ogawa D, Wada J, Yamamoto N, Shikata K, Sato C, Tachibana H, Toyota N, Makino H.
    • Journal Title

      Diabetes

      Volume: 60 Pages: 950-958

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Glucagon-like peptide-1 receptor agonist ameliorates renal injury through its anti-inflammatory action without lowering blood glucose level in a rat model of type 1 diabetes.2011

    • Author(s)
      Kodera R, Shikata K, Kataoka HU, Takatsuka T, Miyamoto S, Sasaki M, Kajitani N, Nishishita S, Sarai K, Hirota D, Sato C, Ogawa D, Makino H.
    • Journal Title

      Diabetologia

      Volume: 54 Pages: 965-978

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] DNETT-Japan Study Group. Diabetic Nephropathy Remission and Regression Team Trial in Japan(DNETT-Japan): Rationale and study design2010

    • Author(s)
      Shikata K, Haneda M, Koya D, Suzuki Y, Tomino Y, Yamada K, Maeda S, Kawakami N, Uzu T, Nishimura M, Sato C, Ogawa D, Makino H
    • Journal Title

      Diabetes Res Clin Pract

      Volume: 87(2) Pages: 228-232

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Relation between estimated glomerular filtration rate and pulse wave velocity in Japanese2010

    • Author(s)
      Miyatake N, Shikata K, Makino H, Numata T
    • Journal Title

      Intern Med

      Volume: 49 Pages: 1315-1320

    • NAID

      130000299533

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Microinflammation is a common risk factor for progression of nephropathy and atherosclerosis in Japanese patients with type 2 diabetes2010

    • Author(s)
      Kajitani N, Shikata K, Nakamura A, Nakatou T, Hiramatsu M, Makino H
    • Journal Title

      Diabetes Res Clin Pract

      Volume: 88 Pages: 171-176

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Relationship between estimated glomerular filtration rate (eGFR) and metabolic syndrome in Japanese.2010

    • Author(s)
      Miyatake N, Shikata K, Makino H, Numata T
    • Journal Title

      Acta Mad Okayama

      Volume: 84 Pages: 202-208

    • NAID

      120002311048

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Diabetic Nephropathy Remission and Regression Team Trial in Japan(DNETT-Japan) : Rationale and study design.2010

    • Author(s)
      Shikata K, Haneda M, Koya D, Suzuki Y, Tomino Y, Yamada K, Maeda S, Kawakami N, Uzu T, Nishimura M, Sato C, Oqawa D.
    • Journal Title

      Diabetes Res Clin Pract. 87

      Pages: 228-232

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Low-Protein Diet Study Group. Long-term effect of modification of dietary protein intake on the p progression of diabetic nephropathy : a randomised controlled trial2009

    • Author(s)
      Koya D, Haneda M, Inomata S, Suzuki Y, Suzuki D, Makino H, Shikata K, Murakami Y, Tomino Y, Yamada K, Araki SI, Kashiwagi A, Kikkawa R
    • Journal Title

      Diabetologia

      Volume: 52 Pages: 2037-2045

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Endothelial barrier protection of FTY720 under hyperglycemic condition : Involvement of focal adhesion kinase, small GTPases and adherens junction proteins2009

    • Author(s)
      Sarai K, Shikata K, Shikata Y, Omori K, Watanabe N, Sasaki M, Nishishita S, Wada J, Goda N, Kataoka N, Makino H
    • Journal Title

      Am J Physiol Cell Physiol

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Endothelial barrier protection by FTY720 under hyperglycemic condition : involvement of focal adhesion kinase, small GTPases, and adherens junction proteins.2009

    • Author(s)
      Sarai K, Shikata K, Shikata Y, Omori K, Watanabe N, Sasaki M, Nishishita S, Wada J, Goda N, Kataoka N, Makino H.
    • Journal Title

      Am J Physiol Cell Physiol. 297

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Advanced glycation end products subspecies-selectively induce adhesion molecule expression and cytokine production in human peripheral blood mononuclear cells.2009

    • Author(s)
      Takahashi HK, Mori S, Wake H, Liu K, Yoshino T, Ohashi K, Tanaka N, Shikata K, Makino H, Nishibori M
    • Journal Title

      J Pharmacol Exp Ther. 330

      Pages: 89-98

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Phenotypic change of macrophages in the progression of diabetic nephropathy ; sialoadhesin-positive activated macrophages are increased in diabetic kidney

    • Author(s)
      Nagase R, Kajitani N, Shikata K, Ogawa D, Kodera R, Okada S, Kido Y, Makino H
    • Journal Title

      Clin Exp Nephrol

      Volume: (In press)

    • NAID

      10031122261

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Presentation] 糖尿病性腎症の治療における新しい展開~Microinflammmationを標的とした治療戦略~2011

    • Author(s)
      四方賢一
    • Organizer
      第34回日本高血圧学会総会
    • Place of Presentation
      宇都宮市
    • Year and Date
      2011-10-21
    • Related Report
      2011 Annual Research Report
  • [Presentation] 糖尿病性腎症治療の最前線2011

    • Author(s)
      四方賢一
    • Organizer
      第26回糖尿病合併症学会
    • Place of Presentation
      大宮市
    • Year and Date
      2011-10-14
    • Related Report
      2011 Annual Research Report
  • [Presentation] 糖尿病性腎症の治療における新しい展開~MIcroinflammationを標的とした治療戦略~2011

    • Author(s)
      四方賢一
    • Organizer
      第75回日本循環器学会
    • Place of Presentation
      横浜市
    • Year and Date
      2011-08-03
    • Related Report
      2011 Annual Research Report
  • [Presentation] Telmisartan attenuates diabetic nephropathy through anti-oxidative and anti-inflammatory actions via activation of peroxisome proliferator-activated recep tor-γ2011

    • Author(s)
      Kajitani N, Shikata K, Kodera R, Miyamoto S, Hirota D, Sato C, Wada J, Ogawa D, and Makino H
    • Organizer
      47th AnnualMeeting of the European Ass ociation for the Study of Diabetes Lisbon Portugal
    • Related Report
      2011 Final Research Report
  • [Presentation] Activation of Peroxisome Proliferator-activated ReceptorδInhibits Streptozotocin-induced Diabetic Nephropathy Through Anti-inflammatory Mechanisms in Mice2011

    • Author(s)
      Tachibana H, Ogawa D, Matsushita Y, Yamamoto N, Toyota N, Sato C, Wada J, Shikata K, Makino H
    • Organizer
      American Diabetes Association 71st Scientific Sessions
    • Place of Presentation
      San Diego, California, USA
    • Related Report
      2011 Final Research Report
  • [Presentation] Activation of Peroxisome Proliferator-activated ReceptorδInhibits Streptozotocin-induced Diabetic Nephropathy Through Anti-inflammatory Mechanisms in Mice2011

    • Author(s)
      Ogawa D, Wada J, Matsushita Y, NakatsukaA, Murakami K, Kanzaki M, Shikata K, Makino H
    • Organizer
      Keystone Symposia
    • Place of Presentation
      Keystone, Colorado, USA
    • Related Report
      2011 Final Research Report
  • [Presentation] PPARδ-mediated anti-inflammatory mechanisms inhibit streptozotocin-induced diabeticnephropathy2010

    • Author(s)
      Ogawa D, Matsushita Y, Shikata K, Wada J, Sato C, Makino H
    • Organizer
      The 2nd Scientific Meeting of the Asian Association for the Study of Diabetes
    • Year and Date
      2010-05-29
    • Related Report
      2011 Final Research Report
  • [Presentation] 糖尿病性腎症の成因としてのMicroinflammation2010

    • Author(s)
      四方賢一
    • Organizer
      第53回日本糖尿病学会
    • Place of Presentation
      ホテルグランヴィア岡山
    • Year and Date
      2010-05-28
    • Related Report
      2010 Annual Research Report
  • [Presentation] Exendin-4a meliorates renal injuries through an ti-oxidative and anti-inflammatory ef fectsin type 1 diabetic rats2010

    • Author(s)
      Kodera. R, Kataoka H, Shikata K, Sato C, Sasa ki M, Nishishita S, Miyamoto S, Hirota D, Kajitani N, Ogawa O, Makino H
    • Organizer
      46th EASD Annualmeeting Stocholm
    • Place of Presentation
      Sweden
    • Related Report
      2011 Final Research Report
  • [Presentation] PPARδ-mediated anti-inflammat orymechanisms inhibit streptozotocin-i nduceddiabetic nephropathy2010

    • Author(s)
      Ogawa D, Matsushita Y, Shikata K, Wada J, Sato C, Makino H
    • Organizer
      ISN-NEXUS K yoto in 2010
    • Place of Presentation
      Kyoto
    • Related Report
      2011 Final Research Report
  • [Presentation] PPARδ-mediated anti-inflammatory mechanisms inhibit streptozotoci n-induced diabetic nephropathy2010

    • Author(s)
      Ogawa D, Matsushita Y, Shikata K, Wada J, Sato C, Makino H
    • Organizer
      Keyston e Symposia
    • Place of Presentation
      Banff, Alberta, Canada
    • Related Report
      2011 Final Research Report
  • [Presentation] 糖尿病とCKD~管理の面から~チーム医療による集約的治療の意義2009

    • Author(s)
      四方賢一
    • Organizer
      第52回日本糖尿病学会年次学術集会 ジョイントシンポジウム4
    • Place of Presentation
      大阪
    • Year and Date
      2009-05-24
    • Related Report
      2009 Annual Research Report
  • [Presentation] Cholecystokinin amelioratesdia betic renal injuries via anti-inflam matory effects2009

    • Author(s)
      Miyamoto S Shikata K Sasaki M Nishishita S Sato C Kataoka H Kodera R Hirota D Kajitani N Makino H
    • Organizer
      45th EASD Annual Meeting
    • Related Report
      2011 Final Research Report
  • [Presentation] Exendin-4 ameliorates renalinjuries through anti-oxidative a nd anti-inflammatory effects in type 1 d iabetic rats2009

    • Author(s)
      Kodera R, Kataoka H, Shikata K, Sato C, Sasaki M, Nishishita S, Miyamoto S, Hirota D, Kajitani N, Ogawa D, Makino H
    • Organizer
      45th EASD Annual meeting
    • Related Report
      2011 Final Research Report
  • [Presentation] Exendin-4 ameliorates renalinjuries through anti-inflammatory effects in type 1 diab etic rats2009

    • Author(s)
      Kodera R, Kataoka H, Shikata K, Makino H
    • Organizer
      Asia Islet Biology and Incretin Symposium(AIBIS)
    • Related Report
      2011 Final Research Report
  • [Book] 慢性合併症の臨床2(腎症) 1.腎症の成因.糖尿病学の進歩2010

    • Author(s)
      四方賢一、槇野博史
    • Publisher
      日本糖尿病学会
    • Related Report
      2011 Final Research Report
  • [Book] 腎不全期糖尿病最新の治療2010

    • Author(s)
      四方賢一
    • Publisher
      南江堂
    • Related Report
      2011 Final Research Report
  • [Book] 糖尿病学の進歩20102010

    • Author(s)
      四方賢一、槇野博史
    • Total Pages
      345
    • Publisher
      診断と治療
    • Related Report
      2010 Annual Research Report
  • [Book] 糖尿病最新の治療2010

    • Author(s)
      四方賢一
    • Total Pages
      310
    • Publisher
      南江堂
    • Related Report
      2009 Annual Research Report

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Published: 2009-04-01   Modified: 2016-04-21  

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