Advanced glycation end products could play an important role of the progression of diabetic nephropathy via epigenetic changes.

• Project/Area Number: 24790866
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Kidney internal medicine
• Research Institution: Kurume University
• Principal Investigator: KAIDA Yusuke 久留米大学, 医学部, 助教 (80441658)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 糖尿病性腎症 / AGEs / 母体 / アルブミン尿 / 酸化ストレス / アディポネクチン / エピジェネティクス / 母体環境 / 腎障害 / エピジェネティック異常

Research Abstract

Overnutrition during perinatal period is known to increase susceptibility to renal injury later in life. Although the precise mechanisms why overnutrition,such as high advanced glycation end products(AGEs) diet,could cause the progression of renal injury later in life remain to be elucidated. Male offspring born to high AGEs fed(high fat diet and high fructose water: HFF) mothers had decreased serum adiponectin compared with male offspring born to normal fed(NF) from day 1 after birth to week 16. HFF had increased serum MDA compared with NF from week 4 after birth. Urinary albumin was increased and enhanced extracellular matrix accumulation was observed in HFF at 16 week. Moreover,HFF significantly upregulated protein expression of TGF-b in the kidney at 16 week. HFF had decreased creatinine clearance compared with NF. Our present data suggest that high AGEs diet could exacerbate renal injury via the oxidative stress and the decrease of adiponectin in male offspring later in life.

Research Products

• [Journal Article] Potential inhibitory effects of L-carnitine supplementation on tissue advanced glycation end products in patients with hemodialysis (2013)
  • Author(s): Fukami K, Yamagishi S, Sakai K, Kaida Y, Adachi T, Ando R, Okuda S
  • Journal Title: Rejuvenation Res. Volume: 16(6) Pages: 460-6
  • Peer Reviewed
• [Journal Article] Involvement of advanced glycation end product-induced asymmetric dimethylarginine generation in endothelial dysfunction (2013)
  • Author(s): Ando R, Ueda S, Yamagishi S, Miyazaki H, Kaida Y, Kaifu K, Yokoro M, Nakayama Y, Obara N, Fukami K, Takeuchi M, Okuda S
  • Journal Title: Diab Vasc Dis Res. Volume: 10(5) Pages: 436-41
  • Peer Reviewed
• [Journal Article] Telmisartan inhibits AGE-induced podocyte damage and detachment (2013)
  • Author(s): Fukami K, Yamagishi S, Kaifu K, Matsui T, Kaida Y, Ueda S, Takeuchi M, Asanuma K, Okuda S
  • Journal Title: MicrovascRes. Volume: 62(9) Pages: 79-83
  • Peer Reviewed
• [Journal Article] DNA Aptamer Raised Against AGEs Blocks the Progression of Experimental Diabetic Nephropathy (2013)
  • Author(s): Kaida Y, Fukami K, Matsui T, Higashimoto Y, Nishino Y, Obara N, Nakayama Y, Ando R, Toyonaga M, Ueda S, Takeuchi M, Inoue H, Okuda S, Yamagishi S
  • Journal Title: Diabetes Volume: 62(9) Pages: 3241-50
  • Peer Reviewed
• [Journal Article] Effects of switching from calcium carbonate to lanthanum carbonate on bone mineral metabolism in hemodialysis patients (2013)
  • Author(s): Manabe R, Fukami K, Ando R, Sakai K, Kusumoto T, Hazama T, Adachi T, Kaida Y, Nakayama Y, Ueda S, Kohno K, Wada Y, Yamagishi S, Okuda S
  • Journal Title: Ther ApherDial Volume: Suppl1 Pages: 35-40
  • Peer Reviewed
• [Journal Article] Evidence for a positive association between serum carnitine and free testosterone levels in uremic men with hemodialysis (2013)
  • Author(s): Sakai K, Fukami K, Yamagishi S, Kaida Y , Adachi T, Ando R, Manabe R, Otsuka A, Sugi K, Ueda S, Okuda S
  • Journal Title: Rejuvenation Res. Volume: 16(3) Pages: 200-5
  • Peer Reviewed
• [Journal Article] Experimental diabetic nephropathy is accelerated in matrix metalloproteinase-2 knockout mice (2013)
  • Author(s): Takamiya Y, Fukami K, Yamagishi S, Kaida Y , Nakayama Y, Obara N, Iwatani R, Ando R, Koike K, Matsui T, Nishino Y, Ueda S, Cooper ME, Okuda S
  • Journal Title: Nephrol Dial Transplant Volume: 28(1) Pages: 55-62
  • Peer Reviewed
• [Journal Article] Experimental diabetic nephropathy is accelerated in matrix metalloproteinase-2 knockout mice. (2013)
  • Author(s): Takamiya Y
  • Journal Title: Nephrol Dial Transplant Volume: 28 Issue: 1 Pages: 55-62
  • DOI: 10.1093/ndt/gfs387
  • Peer Reviewed
• [Journal Article] Decreased serum carnitine is independently correlated with increased tissue accumulation levels of advanced glycation end products in haemodialysis patients (2012)
  • Author(s): Adachi T, Fukami K, Yamagishi S, Kaida Y, Ando R, Sakai K, Adachi H, Otsuka A, Ueda S, Sugi K, Okuda S
  • Journal Title: Nephrology(Carlton) Volume: 17(8) Pages: 689-94
  • Peer Reviewed
• [Journal Article] Proteinuria elevates asymmetric dimethylarginine levels via protein arginine methyltransferase-1 overexpression in a rat model of nephrotic syndrome (2012)
  • Author(s): Kaida Y, Ueda S, Yamagishi S, Nakayama Y, Ando R, Iwatani R, Fukami K, Okuda S
  • Journal Title: Life Sci. Volume: 91(9-10) Pages: 301-5
  • Peer Reviewed
• [Journal Article] Proteinuria elevates asymmetric dimethylarginine levels via protein arginine methyltransferase-1 overexpression in a rat model of nephrotic syndrome. (2012)
  • Author(s): Kaida Y, Okuda S, et al.
  • Journal Title: Life Sci. Volume: 91 Issue: 9-10 Pages: 301-305
  • DOI: 10.1016/j.lfs.2012.06.015
  • Peer Reviewed
• [Journal Article] Decreased serum carnitine is independently correlated with increased tissue accumulation levels of advanced glycation end products in hemodialysis patients. (2012)
  • Author(s): Adachi T
  • Journal Title: Nephrology Volume: 17 Issue: 8 Pages: 689-694
  • DOI: 10.1111/j.1440-1797.2012.01642.x
  • Peer Reviewed
• [Presentation] 高脂肪、高フルクトース負荷によるラット母体環境変化は、アディポネクチン低下に伴い仔の腎障害を惹起する (2014)
  • Author(s): 小原 奈々
  • Organizer: 日本腎臓学会
  • Place of Presentation: パシフィコ横浜