Nuclear receptors as therapeutic targets for diabeticnephropathy.

2012 Fiscal Year Final Research Report

• Project/Area Number: 21249053
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Okayama University
• Principal Investigator: MAKINO Hirofumi 岡山大学, 大学院・医歯薬学総合研究科, 教授 (50165685)
• Co-Investigator(Kenkyū-buntansha): WADA Jun 岡山大学, 大学院・医歯薬学総合研究科, 准教授 (30294408)
• Co-Investigator(Renkei-kenkyūsha): OGAWA Daisuke 岡山大学, 大学院・医歯薬学総合研究科, 准教授 (70535195)
• Project Period (FY): 2009 – 2012
• Keywords: 核内受容体 / 糖尿病性腎症 / レチノイド / 細胞周期 / 糸球体上皮細胞 / PPAR / RXR / LXR

Research Abstract

In the development of diabetic nephropathy, the hypertrophy of renal cells is important for the initial disease process and chronic inflammation further promotes the progression of the disease. Modulator for nuclear receptors may improve these pathological processes. Peroxisome proliferator-activated receptor (PPAR)-δand Liver X receptor (LXR) agonists exerted therapeutic potential by improving inflammation. Retinoid X receptor (RXR) antagonist demonstrated therapeutic potential by correcting cell-cycle abnormalities and cellular hypertrophy. Modulators for nuclear receptors are beneficial for the treatment of diabetic nephropathy.

Research Products

• [Journal Article] Serum galectin-9 levels are elevated in the patients with type 2 diabetes and chronic kidney disease (2013)
  • Author(s): Kurose Y, Wada J, Kanzaki M, Teshigawara S, Nakatsuka A, Murakami K, Inoue K, Terami T, Katayama A, Watanabe M,Higushi C, Eguchi J, Miyatake N, Makino H
  • Journal Title: BMC Nephrol Volume: 14 Pages: 23
  • Peer Reviewed
• [Journal Article] Vaspin inhibits apoptosis of endothelial cells as a ligand for cell-surface GRP78/VDAC complex (2013)
  • Author(s): Nakatsuka A, Wada J, Iseda I, Teshigawara S, Higashio K, Murakami K, Kanzaki M, Inoue K, Terami T, Katayama A, Hida K, Eguchi J, Ogawa D, Matsuki Y, Hiramatsu R, Tagita H, Kakuta S, Iwakura Y, Makino H
  • Journal Title: Circ Res Volume: 112(5) Pages: 771-780
  • Peer Reviewed
• [Journal Article] Telmisartan attenuates diabetic nephropathy by suppressing ixidative stress in db/db mice (2013)
  • Author(s): Sato-Horiguchi C, Ogawa D, Wada J, Tachibana H, Kodera R, Eguchi J, Nakatsuka A, Terami N, Shikata K, Makino H
  • Journal Title: Nephron Exp Nephrol Volume: 121(3-4) Pages: e97-e108
  • Peer Reviewed
• [Journal Article] The effects of telmisartan treatment on the abdominal fat depot in patients with metabolic syndrome and essential hypertension: Abdominal fat Depot Intervention Program of Okayama (ADIPO) (2013)
  • Author(s): Murakami K, Wada J, Ogawa D, Horiguchi CS, Miyoshi T, Sasaki M, Uchida HA, Nakamura Y, Makino H
  • Journal Title: Diab Vasc Dis Res Volume: 10(1) Pages: 93-96
  • Peer Reviewed
• [Journal Article] The serum vaspin levels are reduced in Japanese chronic hemodialysis patients. (2012)
  • Author(s): Inoue J, Wada J, Teshigawara S, Hida K, Nakatsuka A, Takatori U, Kojo S, Akagi S, Nakao K, Miyatake N, McDonald JF, Makino H
  • Journal Title: BMC Nephrol Volume: 13(1) Pages: 163
  • Peer Reviewed
• [Journal Article] Activation of liver x receptor inhibits osteopontin and ameliorates diabetic nephropathy (2012)
  • Author(s): Tachibana H, Ogawa D, Matsushita Y,Bruemmer D, Wada J, Teshigawara S, Eguchi J, Sato-Horiguchi C, Uchida HA, Shikata K, Makino H
  • Journal Title: J Am Soc Nephrol Volume: 23(11) Pages: 1835-1846
  • Peer Reviewed
• [Journal Article] Vaspin is an adipokine ameliorating ER stress in obesity as a ligand for cell-surface GRP78/MTJ-1 complex. (2012)
  • Author(s): Nakatsuka A, Wada J, Iseda I, Teshigawara S, Higashio K, Murakami K, Kanzaki M, Inoue K, Terami T, Katayama A, Hida K, Eguchi J, Horiguchi CS, Ogawa D, Matsuki Y, Hiramatsu R, Yagita H, Kakuta S, Iwakura Y, Makino H
  • Journal Title: Diabetes Volume: 61(11) Pages: 2823-2832
  • Peer Reviewed
• [Journal Article] The therapeutic potential of synthetic human atrial natriuretic peptide in nephrotic syndrome: a randomized controlled trial. (2012)
  • Author(s): Kanzaki M, Wada J, Kikumoto Y, Akagi S, Nakao K, Sugiyama H, Makino H
  • Journal Title: Int J Nephrol Renovasc Dis Volume: 5 Pages: 91-96
  • Peer Reviewed
• [Journal Article] Hydrogen-rich water prevents progression of non-alcoholic steatohepatitis and accompanying hepatocarcinogenesis in mice. (2012)
  • Author(s): Kawai D, Takaki A, Nakatsuka A, Wada J, Tamaki N, Yasunaka T, Koike K, Tsuzaki R, Matsumoto K, Miyake Y, Shiraha H, Morita M, Makino H, Yamamoto K
  • Journal Title: Hepatology Volume: 56(3) Pages: 912-921
  • Peer Reviewed
• [Journal Article] Serum vaspin concentrations are closely related to insulin resistance and rs77060950 at SERPINA12 genetically defines distinct group with higher serum levels in Japanese population. (2012)
  • Author(s): Teshigawara S, Wada J, Hida K, Nakatsuka A, Eguchi J, Murakami K, Kanzaki M, Inoe K, Terami T, Katayama A, Iseda I, Matsushita Y, Miyatake N, McDonald JF, Hotta K, Makino H
  • Journal Title: J Clin Endocrinol Metab Volume: 97(7) Pages: E1202-1207
  • Peer Reviewed
• [Journal Article] Galectin-9 and T cell immunoglobulin mucin-3 pathway is a therapeutic target for type 1 diabetes (2012)
  • Author(s): Kanzaki M, Wada J, Sugiyama K, Nakatsuka A, Teshigawara S, Murakami K, Inoue K, Terami T, Katayama A, Eguchi J, Akiba H, Yagita H, Makino H
  • Journal Title: Endocrinology Volume: 153(2) Pages: 612-620
  • Peer Reviewed
• [Journal Article] Impact of circulating vaspin levels on metabolic variables in elderly twins (2012)
  • Author(s): Hida K, Poulsen P, Teshigawara S, Nilsson E, Friedrichsen M, Ribel-Madsen R, Grunnet L, Lund SS, Wada J, Vaag A
  • Journal Title: Diabetologia Volume: 55(2) Pages: 530-532
  • Peer Reviewed
• [Journal Article] RXR antagonism induces G0/G1 cell cycle arrest and ameliorates obesity by up-regulating the p53-p21^Cip1pathway in adipocytes. (2012)
  • Author(s): Nakatsuka A, Wada J, Hida K, Hida A, Eguchi J, Teshigawara S, Murakami K, Kanzaki M, Inoue K, Terami T, Katayama A, Ogawa D, Kagechika H, Makino H
  • Journal Title: J Pathol Volume: 226(5) Pages: 784-795
  • Peer Reviewed
• [Journal Article] High glucose increases metallothionein expression in renal proximal tubular epithelial cells. (2011)
  • 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 Volume: 2011 Pages: 534872
  • Peer Reviewed
• [Journal Article] Icodextrin increases technique survival rate in peritoneal dialysis patients with diabetic nephropathy by improving body fluid management: a randomized controlled trial. (2011)
  • Author(s): Takatori Y, Akagi S, Sugiyama H, Inoue J, Kojo S, Morinaga H, Nakao K, Wada J, Makino H
  • Journal Title: Clin J Am Soc Nephrol Volume: 6(6) Pages: 1337-1344
  • Peer Reviewed
• [Journal Article] Activation of Peroxisome Proliferator-Activated Receptor δInhibits 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(3) Pages: 960-968
  • Peer Reviewed
• [Journal Article] P-selectin glycoprotein ligand-1 deficiency is protective against obesity-related insulin resistance (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(1) Pages: 189-99
  • Peer Reviewed
• [Journal Article] In vivo delivery of gremlin siRNA plasmid reveals therapeutic potential against diabetic nephropathy by recovering bone morphogenetic protein-7. (2010)
  • Author(s): Zhang Q, Shi Y, Wada J, Malakauskas SM, Liu M, Ren Y, Du C, Duan H, Li Y, Li Y, Zhang Y
  • Journal Title: PLoS ONE Volume: 5(7) Pages: e11709
  • Peer Reviewed
• [Journal Article] Effects of icodextrin peritoneal dialysis solution on the peritoneal membrane in the STZ-induced diabetic rat model with partial nephrectomy (2010)
  • Author(s): Nakao A, Nakao K, Takatori Y, Kojo S, Inoue J, Akagi S, Sugiyama H, Wada J, Makino H
  • Journal Title: Nephrol Dial Transplant Volume: 25(5) Pages: 1479-1488
  • 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 Volume: 297(4) Pages: C945-54
  • Peer Reviewed
• [Presentation] Renin angiotensin system inhibition in diabetic nephropathy. (2012)
  • Author(s): Makino H:
  • Organizer: ASN Kidney Week 2012
  • Place of Presentation: San Diego, CA, USA
  • Year and Date: 2012-11-02
• [Presentation] Basic mechanism underlying diabetic nephropathy and CKD. (2011)
  • Author(s): Makino H:
  • Organizer: World Congress of Nephrology
  • Place of Presentation: Vancouver, Canada
  • Year and Date: 2011-04-11
• [Presentation] 全身を制御する腎臓-33年の腎臓研究を顧みて- (2010)
  • Author(s): 槇野博史
  • Place of Presentation: 神戸市
  • Year and Date: 2010-06-17
• [Presentation] Thiazolidinediones and diabetic nephropathy (2009)
  • Author(s): Makino H
  • Organizer: World Congress of Nephrology
  • Place of Presentation: Milan, Italy
  • Year and Date: 2009-05-22