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

晚期糖基化终末产物可能通过表观遗传变化在糖尿病肾病的进展中发挥重要作用。

• 批准号: 24790866
• 负责人: KAIDA Yusuke
• 金额: $ 2万
• 依托单位: Kurume University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2012
• 资助国家: 日本
• 起止时间: 2012-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-24790866/
• 关键词: 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

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.

围产期营养过剩已知会增加以后生活中肾损伤的易感性。尽管营养过剩的确切机制，如高晚期糖基化终产物（AGEs）饮食，可能导致生命后期肾损伤的进展仍有待阐明。高AGEs喂养（高脂肪饮食和高果糖水：HFF）的母亲所生的雄性后代与正常喂养（NF）的雄性后代相比，从出生后第1天到第16周，血清脂联素降低。从出生后第4周开始，HFF与NF相比血清MDA升高。16周时，HFF患者尿白蛋白升高，细胞外基质积累增强。此外，HFF在16周时显著上调肾脏中TGF-b的蛋白表达。与NF相比，HFF降低了肌酐清除率。我们目前的数据表明，高AGEs饮食可能通过氧化应激和脂联素的降低加剧雄性后代的肾损伤。

项目成果

Experimental diabetic nephropathy is accelerated in matrix metalloproteinase-2 knockout mice.

• DOI: 10.1093/ndt/gfs387
• 发表时间: 2013
• 期刊: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
• 作者: Y. Takamiya;K. Fukami;S. Yamagishi;Y. Kaida;Yosuke Nakayama;Nana Obara;Ryuji Iwatani;Ryotaro Ando;Kiyomi Koike;T. Matsui;Yuri Nishino;S. Ueda;M. Cooper;S. Okuda

Potential Inhibitory Effects of L-Carnitine Supplementation on Tissue Advanced Glycation End Products in Patients with Hemodialysis

• DOI: 10.1089/rej.2013.1459
• 发表时间: 2013-12-01
• 期刊: REJUVENATION RESEARCH
• 影响因子: 2.6
• 作者: Fukami, Kei;Yamagishi, Sho-ichi;Okuda, Seiya
• 通讯作者: Okuda, Seiya

Decreased serum carnitine is independently correlated with increased tissue accumulation levels of advanced glycation end products in haemodialysis patients

• DOI: 10.1111/j.1440-1797.2012.01642.x
• 发表时间: 2012-11-01
• 期刊: NEPHROLOGY
• 影响因子: 2.5
• 作者: Adachi, Takeki;Fukami, Kei;Okuda, Seiya
• 通讯作者: Okuda, Seiya

Telmisartan inhibits AGE-induced podocyte damage and detachment

• DOI: 10.1016/j.mvr.2013.04.006
• 发表时间: 2013-07-01
• 期刊: MICROVASCULAR RESEARCH
• 影响因子: 3.1
• 作者: Fukami, Kei;Yamagishi, Sho-ichi;Okuda, Seiya
• 通讯作者: Okuda, Seiya

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

由于高脂肪和高果糖负荷而引起的大鼠母体环境的变化，会因脂联素减少而导致后代肾脏损伤。

• 发表时间: 2014
• 作者: Kaida Y;Okuda S;et al.;Adachi T;小原 奈々
• 通讯作者: 小原 奈々