The role of Azgp-1, candidate gene for obesity, in CKD with metabolic syndrome

• Project/Area Number: 21700701
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Applied health science
• Research Institution: Juntendo University
• Principal Investigator: HAGIWARA Shinji Juntendo University, 医学部, 助教 (70445568)
• Co-Investigator(Kenkyū-buntansha): TANIMOTO Mituo , 医学部, 助教 (00420836)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2009: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: メタボリックシンドローム / 慢性腎臓病 / Azgp-1 / Zinc-alpha2-glycoprotein (Azgp-1) / PPARγ / Zinc-alpha2-glycoprotein(Azgp-1)

Research Abstract

In this study, we identified the localization of Azgp-1 expression in the kidney of spontaneous type 2 diabetic obesity KK/Ta mouse, analyzed the function of Azgp-1 in the kidney and examined the role of Azgp-1 on CKD with metabolic syndrome.
The expressions of Azgp-1 protein were increased at tubular epithelial cells of KK/Ta mice compared to BALBc mice. There are no expressions of Azgp-1 protein in the kidney of STZ induced diabetic BALBc mice. The Azgp-1 mRNA expressions were decreased in the kidney of high fat diet C57BL/6 mice. The Azgp-1 mRNA expressions were increased in the kidney of KK/Ta mice treated by Pioglitazone. The concentrations of urinary Azgp-1 protein were significantly increased in patients with type 2 diabetes and positively correlated with glomerular filtration rate (GFR), urinary albumin creatinine ratio and urinary NAG creatinine ratio.
Azgp-1 protein expressions were increased in proximal tubular epithelial cells of diabetic nephropathy, probably related to lipid metabolism and transcript factor PPAR-γ is a modulator of Azgp-1 in the kidney. Moreover, it is suggested that the concentrations of urinary Azgp-1 is useful as a new urinary biomarker in type 2 diabetic nephropathy patients.

Research Products

• [Journal Article] Attenuating effect of angiotensin-(1-7) on angiotensin II-mediated NAD(P)H oxidase activation in type 2 diabetic nephropathy of KK-Ay/Ta mice. (2011)
  • Author(s): Moon JY, Tanimoto M, Gohda T, Hagiwara S, Yamazaki T, Ohara I, Murakoshi M, Aoki T, Ishikawa Y, Lee SH, Jeong KH, Lee TW, Ihm CG, Lim SJ, Tomino Y.
  • Journal Title: Am J Physiol Renal Physiol. In press.
• [Journal Article] Attenuating effect of angiotensin-(1-7) on angiotensin II-mediated NAD(P)Hoxidase activation in type 2 diabetic nephropathy of KK-Ay/Ta mice. (2011)
  • Author(s): Moon JY, Tanimoto M, Gohda T, Hagiwara S, Yamazaki T, Ohara I, Murakoshi M, Aoki T, Ishikawa Y, Lee SH, Jeong KH, Lee TW, Ihm CG, Lim SJ, Tomino Y.
  • Journal Title: Am J Physiol Renal Physiol. Volume: (In press)
  • Peer Reviewed
• [Journal Article] Mindin : a novel marker for podocyte injury in diabetic nephropathy. (2010)
  • Author(s): Murakoshi M, Tanimoto M, Gohda T, Hagiwara S, Takagi M, Horikoshi S, Tomino Y.
  • Journal Title: Nephrol Dial Transplant. In press.
• [Journal Article] Effect of Combination Therapy with Angiotensin Receptor Blocker and 1,25-Dihydroxyvitamin D(3) in Type 2 Diabetic Nephropathy in KK-A/Ta Mice. (2010)
  • Author(s): Ohara I, Tanimoto M, Gohda T, Yamazaki T, Hagiwara S, Murakoshi M, Aoki T, Toyoda H, Ishikawa Y, Funabiki K, Horikoshi S, Tomino Y.
  • Journal Title: Nephron Exp Nephrol 117 Pages: 124-132
• [Journal Article] Mindin : a novel marker for podocyte injury in diabetic nephropathy. (2010)
  • Author(s): Murakashi M, Tanimoto M, Gohda T, Hagiwara S, Takagi M, Horikoshi S, Tomino Y.
  • Journal Title: Nephrol Dial Transplant. Volume: (In press)
  • Peer Reviewed
• [Journal Article] Effect of Combination Therapy with Angiotensin Receptor Blocker and 1,25-Dihydroxyvitamin D(3) in Type 2 Diabetic Nephropathy in KK-A/Ta Mice. (2010)
  • Author(s): Ohara I, Tanimoto M, Gohda T, Yamazaki T, Hagiwara S, Murakoshi M, Aoki T, Toyoda H, Ishikawa Y, Funabiki K, Horikoshi S, Tomino Y.
  • Journal Title: Nephron Exp Nephrol. Volume: 117 Pages: 124-132
  • Peer Reviewed
• [Journal Article] Combination effects of enalapril and losartan on lipid peroxidation in the kidneys of KK-Ay/Ta mice. (2009)
  • Author(s): Yamazaki T, Tanimoto M, Gohda T, Ohara I, Hagiwara S, Murakoshi M, Matsumoto M, Kaneko S, Aoki T, Toyoda H, Ishikawa Y, Funabiki K, Horikoshi S, Tomino Y.
  • Journal Title: Nephron Exp Nephrol 113 Pages: 66-76
• [Journal Article] Effects of pyridoxamine (K-163) on glucose intolerance and obesity in high-fat diet C57BL/6J mice. (2009)
  • Author(s): Hagiwara S, Gohda T, Tanimoto M, Ito T, Murakoshi M, Ohara I, Yamazaki T, Matsumoto M, Horikoshi S, Funabiki K, Tomino Y.
  • Journal Title: Metabolism 58 Pages: 934-945
• [Journal Article] 炭酸ランタン(リン吸着薬)の血清中リン結合作用の検討 (2009)
  • Author(s): 奥村こずえ, 谷本光生, 萩原晋二, 濱田千江子, 堀越哲, 富野康日己
  • Journal Title: Nephrology Frontier 8 Pages: 314-317
• [Journal Article] Effects of pyridoxamine (K-163) on glucose intolerance and obesity in high-fat diet C57BL/6J mice. (2009)
  • Author(s): Hagiwara S, Gohda T, Tanimoto M, Ito T, Murakoshi M, Ohara I, Yamazaki T, Matsumoto M, Horikoshi S, Funabiki K, Tomino Y.
  • Journal Title: Metabohsm 58 Pages: 934-945
  • Peer Reviewed
• [Presentation] 2型糖尿病腎症におけるZinc-alpha2-glycoprotein(Azgp-1)の役割の検討 (2010)
  • Author(s): 萩原晋二、合田朋仁、谷本光生、古川雅子、村越真紀、石川祐史、青木竜弥、表敬介、山口早織、堀越哲、富野康日己
  • Organizer: 第53回日本腎臓学会学術総会
  • Place of Presentation: 神戸
  • Year and Date: 2010-06-16
• [Presentation] 高脂肪食C57BL/6マウスにおけるPyridoxamine投与による耐糖能障害・肥満改善効果の検討 (2010)
  • Author(s): 萩原晋二、合田朋仁、村越真紀、谷本光生、古川雅子、石川祐史、青木竜弥、表敬介、山口早織、蒔田雄一郎、船曳和彦、堀越哲、富野康日己
  • Organizer: 第53回日本糖尿病学会年次学術集会
  • Place of Presentation: 岡山
  • Year and Date: 2010-05-28
• [Book] 腎機能低下患者への薬の使い方2版 (2011)
  • Author(s): 富野康日己, 他(萩原晋二)
  • Total Pages: 294
  • Publisher: 株式会社医学書院
• [Book] 腎機能低下患者への薬の使い方 2版 (2011)
  • Author(s): 富野康日己, 他(萩原晋二)
  • Total Pages: 294
  • Publisher: 株式会社 医学書院
• [Remarks] ホームページ等
• [Patent(Industrial Property Rights)] 慢性腎疾患の診断方法 (2010)
  • Inventor(s): 村越真紀、萩原晋二、谷本光生、合田朋仁、富野康日己
  • Industrial Property Rights Holder: 学校法人順天堂
  • Filing Date: 2010-01-07
• [Patent(Industrial Property Rights)] 慢性腎疾患の診断方法 (2010)
  • Inventor(s): 村越真紀、萩原晋二、谷本光生、合田朋仁、富野康日己
  • Industrial Property Rights Holder: 学校法人順天堂
  • Industrial Property Number: 2010-001638
  • Filing Date: 2010-01-07