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：1994年，我们首先证明了载脂蛋白（APO）Eε2等位基因与糖尿病性apo apo e2有助于高血浆脂肪素的目的。在遗传多态性，残留的脂蛋白和糖尿病性肾病之间。受试者和mitchods：2个在10年内糖尿病持续时间的糖尿病患者分为3个apo e2（n = 22），e3 /3 = e3 /3（n = 22） 102）和E4（n = 34）。 Apo E2糖尿病在Apo E3/3（34.3％）或APO E4患者（8.8％）中han，并且Apo E3/3和E4组之间的明显肾病也存在显着差异。 Apo E2患者的明显高，Apo E4患者显着高于In in in in。与APO A3 /3-IDL相比， - IIDL刺激了TLY PKC活性，TGF-B合成和IV型胶原蛋白和纤连蛋白合成。