Apical cell membranes are shed into urine from injured podocytes: A novel phenomenon of podocyte injury
Apical cell membranes are shed into urine from injured podocytes: A novel phenomenon of podocyte injury
复制标题
DOI：
10.1681/asn.2004070564
复制
发表时间：
2005-02-01
影响因子：
13.6
通讯作者：
Kajita, T
中科院分区：
文献类型：
--
作者：
Hara, M;Yanagihara, T;Kajita, T
以往的研究表明，肾炎患者的尿液中含有足细胞及其碎片(足细胞[PCX]阳性颗粒结构[PPGS])，反映足细胞损伤的程度。本研究旨在追踪PPGS的起源。应用免疫组织化学方法对53例肾病综合征和肾炎患儿的尿液和肾活检标本进行检测。用抗PCX抗体对肾脏切片的免疫荧光研究表明，PPGS起源于肾小球并流入管腔。电子显微镜检查显示，PPGS起源于肾小球受损足细胞上的微绒毛或囊泡样结构。为了研究PPGS的起源，对足细胞的顶端、裂隙-横隔部和基底部进行了特殊染色，揭示了PPGS主要由顶端足细胞膜组成。几种新开发的抗体与PCX分子的不同片段发生反应，用来分析更详细的膜结构，发现PPGS含有完整的PCX分子，表明细胞膜结构是从尿液中排出的。PCX含量和足细胞数量的定量结果显示，正常对照组肾小球每足细胞尿沉淀物PCX(u-sed-PCX)含量远高于正常肾小球的PCX含量，提示u-sed-PCX不只来自分离足细胞的细胞碎片。Use-PCX与肾组织学的相关性分析表明，PPGS的存在反映了急性肾小球损伤。总而言之，足细胞顶端细胞膜从受损的足细胞脱落到尿液中，这表明这是一种以前未被发现的足细胞损伤的表现。
Previously it was shown that urine from patients with nephritis contains podocytes and their fragments (podocalyxin [PCX]-positive granular structures [PPGS]), reflecting the degree of podocyte injury. The present study was designed to trace PPGS to their origin. Urine samples and renal biopsy specimens from 53 children with nephrotic syndrome and nephritis were examined immunohistochemically. Immunofluorescence studies of kidney sections using an anti-PCX antibody demonstrated that PPGS originated from the glomerulus and flowed into the tubular lumen. Electron microscopic examination revealed that PPGS originated from microvillous or vesicle-like structures on injured podocytes in the glomerulus. For examining the origin of the PPGS, apical, slit-diaphragmatic, and basal portions of the podocytes were specifically stained, revealing that PPGS are composed primarily of apical podocyte membranes. Several newly developed antibodies that are reactive with various segments of the PCX molecule were used to analyze more detailed membrane structures, and it was found that PPGS contained intact PCX molecules, indicating that cell membrane structures are excreted in urine. The quantification of PCX content and podocyte numbers revealed that urinary sediment PCX (u-sed-PCX) content per urinary podocyte was much higher than PCX content per podocyte from isolated glomeruli of normal controls, suggesting that u-sed-PCX are derived from sources other than just the cell debris of detached podocytes. Analysis of the correlation between u-sed-PCX and renal histology revealed that the presence of PPGS reflects acute glomerular injury. In conclusion, podocyte apical cell membranes are shed into the urine from injured podocytes, indicating a previously unrecognized manifestation of podocyte injury.