Does undernutrition during development program renal glomerular injury and hypertension? -From animal studies to patients

肾发育过程中营养不良是否会导致肾小球损伤和高血压？

• 批准号: 21390307
• 负责人: NISHIMURA Hiroko
• 金额: $ 11.23万
• 依托单位: Niigata University of Health and Welfare (2011)Niigata University (2009-2010)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21390307/
• 关键词: Fetal programming; ポドサイトスリット膜; 腎糸球体障害; 巣状系球体硬化症; ニホンウズラ; 低出生体重児; 子宮内発育阻害; 高血圧; 糸球体硬化症; 胎生期低栄養; メサンギウム細胞増殖; 発育障害; Apoptosis; 巣状糸球体硬化症; 賢系球体障害

In advanced countries, the number of low birth weight (LBW) babies increased. Moreover, adverse events during development increase vulnerability tocardiovascular and renal disease in later life. To determine whether reduced nutrition duringdevelopment leads to focal segmental glomeruloscleorsis (FSGS), we conducted translationalresearch from an avian model to children diagnosed by renal biopsies. Japanese quail in which5-10% egg white was withdrawn (EwW) before incubation had lower BW than controls. EwWbirds also had a reduced hatching rate and smaller glomeruli. Furthermore, plasmaglucocorticoid levels and glomerular apoptosis were higher in perinatal EwW quail, leading tothe decrease in number of glomeruli in adult. In glomerular podocytes from mature EwW quail,intercellular adhesion molecules and slit diaphragms were well maintained, whereas capillaryloops showed focal ballooning; laminin-positive substance was accumulated in the mesangium.Thirty-three percent (33%) of chidren diagnosed by renal biopsies (n = 206) conducted atNiigata University since 1990 as having FSGS (n = 15) had LBW. The LBW-FSGS childrenshowed glomeruli with sclerotic lesions significantly more than normal BW-FSGS children, andthe number of podocytes was lower. Damaged or incompletely mature mesangium providesreduced architectural support and may trigger the nephrosclerosis. The results from the animalexperiments agree with the clinical observations. LBW may be deemed a risk factor for FSGS.

在发达国家，低出生体重（LBW）婴儿的数量有所增加。此外，发育期间的不良事件会增加晚年患心血管和肾脏疾病的易感性。为了确定发育过程中营养减少是否会导致局灶性节段性肾小球硬化（FSGS），我们进行了从禽类模型到肾脏活检诊断的儿童的转化研究。孵育前提取5-10%蛋清的鹌鹑体重低于对照组。雏鸟的孵化率也较低，肾小球较小。此外，围产期EwW鹌鹑的血浆糖皮质激素水平和肾小球凋亡水平较高，导致成年后肾小球数量减少。成熟EwW鹌鹑肾小球足细胞细胞间黏附分子和狭缝膈维持良好，毛细血管袢呈局灶性球囊；层粘连蛋白阳性物质积聚于系膜。自1990年以来在新泻大学进行的肾脏活检诊断为FSGS的儿童（n = 206）中有33%（33%）患有LBW。LBW-FSGS患儿肾小球硬化病变明显多于正常BW-FSGS患儿，足细胞数量减少。受损或不完全成熟的系膜提供减少的结构支持，并可能引发肾硬化。动物实验结果与临床观察一致。LBW可能被视为FSGS的一个风险因素。

项目成果

成人病は胎生期から始まるー動物実験から臨床までー

成人疾病始于胚胎期——从动物实验到临床实践——

• 作者: Mastumoto M;Yasuda;K;Kubo M;Yoshimoto T;Nakanishi K.;Nishimura H
• 通讯作者: Nishimura H

Enhanced apoptosis may lead to fewer nephrons in Japanese quail subjected to reduced nutrition during development

细胞凋亡增强可能导致日本鹌鹑在发育过程中营养减少，肾单位减少

• 发表时间: 2013
• 作者: Okumura A;Uematsu M;Imataka G;Tanaka M;OkanishiT;KubotaT;SudoA;Tohyama J;Tsuji M;Ohmori I;Naiki M;Hiraiwa-Sofue A;Sato H;Saitoh S;Shimizu T;Urabe M;Nishimura H
• 通讯作者: Nishimura H

Does undernutrition program renal glomerular injury leading to focal segmental glomerulosclerosis?

营养不良是否会导致肾小球损伤导致局灶节段性肾小球硬化？

• 发表时间: 2011
• 作者: Kubo M;Motomura Y;Tanaka S;Suzuki Y;Inoue H;Miyatake s;Nishimura H
• 通讯作者: Nishimura H

Classical cadherins and catenins expressed in the podocyte

足细胞中表达的经典钙粘蛋白和连环蛋白

• 发表时间: 2011
• 期刊: J Developmental Nephrology
• 作者: Yaoita E

Fetal origins of adultdiseases: From animal studies topatients

成人疾病的胎儿起源：从动物研究到患者

• 发表时间: 2012
• 作者: Mizukami;H.;Hayashi K;Nishimura H
• 通讯作者: Nishimura H