Study on the mechanism by which apolipoprotein(apo) E2 promotes diabetic nephropathy

载脂蛋白(apo)E2促进糖尿病肾病的机制研究

基本信息

批准号：
14571112
负责人：
ETO Masaaki
金额：
$ 1.66万
依托单位：
Kawasaki Medical School
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2003
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14571112/
关键词：
diabetic nephropathy apo E2 apolipoprotein apo E genotype remnant lipoproteins TGF-b mesangial cells PKC activity アポリポプロテインE 危険因子 PKC TGF-β

项目摘要

Background and Aim : In 1994 we first demonstrated that the apolipoprotein(apo) E ε2 allele is associated with the progression of diabetic nephropathy. Apo E2 is well known to contribute to high plasma levels of remnant lipoproteins. The aim of the present study is to further investigate the association between apo E genetic polymorphism, remnant lipoproteins and diabetic nephropathy.Subjects and Methods : Type 2 diabetic patients who had a diabetes duration over 10 years were divided into the 3 apo E groups ; apo E2(n=22),E3/3(n=102) and E4(n=34). Plasma levels of lipids and remnant lipoproteins were measured. Histologic studies were performed using renal biopsy specimens in apo E2 patient. The effects of apo E2-IDL(remnant lipoproteins) on cultured human mesangial cells were studied.Results : The frequency of overt nephropathy was significantly higher in apo E2 diabetic patients(59.1%) than in apo E3/3(34.3%) or apo E4 patients(8.8%), and there was also a significant difference in the frequency of overt nephropathy between apo E3/3 and E4 groups. Plasma levels of triglyceride and remnant-like lipoprotein particles(RLP)-chol and were significantly higher in apo E2 patients, and significantly lower in apo E4 patients than in apo E3/3 patients. Logistical regression analysis showed that odds ratios of high plasma remnant(RLP-C≧5.2mg/dl) for the presence of overt nephropathy were 3.614(p=0.0208). Histological renal change of apo E2 patient was almost identical to diabetic nephropathy. Immunohistochemically, apo E and apo B were stained in glomerulus of apo E2 patient. Apo E2-IDL stimulated significantly PKC activity, TGF-b synthesis, and type IV collagen and fibronectin synthesis in mesangial cells sa compared with apo E3/3-IDL.Conclusion : Remnant lipoproteins may have an important role in the progression of diabetic nephropathy.

背景和目的：1994年，我们首先证明了载脂蛋白（APO）Eε2等位基因与糖尿病肾病的进展有关。众所周知，APO E2有助于高血浆脂蛋白水平。本研究的目的是进一步研究APO遗传多态性，残余脂蛋白和糖尿病性肾病之间的关联。对象和方法：在10年内糖尿病持续时间的2型糖尿病患者分为3个APO E组； APO E2（n = 22），E3/3（n = 102）和E4（n = 34）。测量脂质和残留脂蛋白的血浆水平。在APO E2患者中使用肾脏活检标本进行了组织学研究。研究了Apo E2-IDL（残留脂蛋白）对培养的人类弥赛亚细胞的影响。反应：Apo E2糖尿病患者（59.1％）明显高于APO E3/3/3/3（34.3％）或APO E4患者（8.8％）（8.8％）（8.8％）（8.8％）的频率（8.8％）的频率（59.1％）的频率明显高于Apo E2糖尿病患者（59.1％），并且频率是显着差异。 E4组。 APO E2患者的血浆甘油三酸酯和残留样脂蛋白颗粒（RLP） - 胆碱水平明显更高，而APO E4患者的水平明显低于APO E3/3患者。后勤回归分析表明，对于明显的肾病，高血浆残留物（RLP-C≧5.2mg/dL）的优势比为3.614（p = 0.0208）。 Apo E2患者的组织学肾变量几乎与糖尿病性肾病相同。免疫组织化学，将APO E和APO B染色在Apo E2患者的肾小球中。与APO E3/3-IDL相比，APO E2-IDL显着刺激了PKC活性，TGF-B合成，IV型胶原蛋白和纤连蛋白合成。结论：残留的脂蛋白可能在糖尿病肾病的进展中具有重要作用。