GLOMERULAR DAMAGE AFTER UNINEPHRECTOMY IN YOUNG-RATS .2. MECHANICAL-STRESS ON PODOCYTES AS A PATHWAY TO SCLEROSIS
GLOMERULAR DAMAGE AFTER UNINEPHRECTOMY IN YOUNG-RATS .2. MECHANICAL-STRESS ON PODOCYTES AS A PATHWAY TO SCLEROSIS
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DOI：
10.1038/ki.1992.272
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发表时间：
1992-07-01
影响因子：
19.6
通讯作者：
KRIZ, W
中科院分区：
文献类型：
--
作者：
NAGATA, M;KRIZ, W
在之前的研究[1]中，我们发现在年轻大鼠UNX后6个月内，残余肾脏中的肾小球发生一系列严重变化，最终导致局灶性节段性肾小球硬化（FGS）。异常形状的毛细血管通道的形成被证明是由局部系膜衰竭引起的，并且被认为是更严重病变发展的病灶。在本文件中。描述并分析了足细胞结构中特征性病变的发展。伴随着UNX后的总体肾小球生长，观察到足细胞明显肥大，而每个肾小球的足细胞平均数没有变化。足细胞似乎不能维持与整个毛簇相同程度的生长;足细胞肥大后很快发生适应不良的变化，最终导致细胞破坏。病理变化的顺序如下：细胞体体积和面积增大，细胞质片层明显变薄。初级突起变薄，经常延伸到远处的毛细血管。作为一个整体，毛细血管面积由一个单一的足细胞是显着扩大。此外，扩张的细胞质片（来自足细胞胞体）覆盖了越来越大比例的毛细血管外表面，即过滤面积。因此，增加量的滤液被递送到亚细胞体空间中。由于滤液流出受阻而进入泌尿腔，导致细胞质层膨出形成假性囊肿。覆盖在异常形状和扩张的毛细血管通道上的足细胞通常受到最严重的影响。簇状肥大、假性囊肿形成和局部毛细血管扩张导致足细胞广泛附着于Bowman囊。贴附是毛簇粘附力发展的先决条件。足细胞从这些区域中的GBM的局部脱离允许壁细胞进入GBM。在早期粘连中，簇与鲍曼氏囊的连接是通过附着在GBM和鲍曼氏囊基底膜上的单个壁细胞建立的。粘连被认为是节段性硬化的病灶：随着粘连的进展。相关的簇状区域变成硬化。在目前的模式FGS开发专门领域的簇绒粘合。
In a preceding study [1], we showed that within six months after UNX in young rats, glomeruli in the remnant kidney undergo a sequence of serious changes which finally lead to focal segmental glomerulosclerosis (FGS). The formation of abnormally-shaped capillary channels was shown to result from local mesangial failure and is considered to be a nidus for the development of more severe lesions. In the present paper. the development of characteristic lesions in podocyte structure is described and analyzed. Concomitant with overall glomerular growth after UNX, a pronounced hypertrophy of podocytes was observed, while the mean number of podocytes per glomerulus did not change. It appears that podocytes cannot sustain the same degree of growth as the tuft as a whole; podocyte hypertrophy is soon followed by maladaptive changes which eventually lead to cell destruction. The following sequence of pathologic changes can be suggested: cell bodies enlarge in volume and area associated with a dramatic attenuation to cytoplasmic sheets. Primary processes are thinned out and frequently extend to remote capillaries. As a whole, the capillary area served by a single podocyte is dramatically enlarged. Furthermore, the expanding cytoplasmic sheets (derived from podocyte cell bodies) cover an increasingly large proportion of the outer capillary surface, that is, of the filtration area. Consequently, an increasing amount of filtrate is delivered into the subcellbody space. Obstruction of the efflux of this filtrate into the urinary space causes bulging of the overlying cytoplasmic sheets into pseudocysts. Podocytes overlying abnormally-shaped and dilated capillary channels are generally the most seriously affected. Tuft hypertrophy, pseudocyst formation and local capillary expansion cause widespread apposition of podocytes to Bowman's capsule. Appositions are a prerequisite for the development of tuft adhesion. Local detachment of a podocyte from the GBM in those areas allows access of parietal cells to the GBM. In early adhesions the connection of the tuft to Bowman's capsule is established by single parietal cells which attach to both the GBM and the basement membrane of Bowman's capsule. An adhesion is considered as a nidus for segmental sclerosis: as the adhesion progresses. the related tuft regions turn into sclerosis. In the present model FGS develops exclusively in areas of tuft adhesion.