Deletion of Cd151 results in a strain-dependent glomerular disease due to severe alterations of the glomerular basement membrane
Deletion of Cd151 results in a strain-dependent glomerular disease due to severe alterations of the glomerular basement membrane
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DOI：
10.2353/ajpath.2008.071149
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发表时间：
2008-10-01
影响因子：
6
通讯作者：
Roselli, Severine
中科院分区：
文献类型：
--
作者：
Baleato, Rosa M.;Guthrie, Petrina L.;Roselli, Severine
在人类和小鼠中，CD151的改变都与原发性肾小球疾病有关，这意味着CD151是肾小球滤过屏障的关键组成部分。CD151属于Tetraspanin家族，与细胞-基质黏附复合体如α-3，β，1-整合素相关。在这里，我们展示了CD151缺陷小鼠在FVB背景下发生严重的肾脏疾病，但在B6背景下是健康的。为识别调节蛋白尿的基因提供了一种新的和独特的工具。为了更好地了解CD151在肾脏中的功能，我们研究了它在CD151缺失肾脏中的表达模式和早期超微结构缺陷。CD151在小鼠肾的足细胞中表达，并与α3-整合素共同定位于足细胞足突的底部、肾小球基底膜的锚定部位。有趣的是，在CD151缺失的肾脏中，蛋白尿开始时的第一个超微结构损害是基底膜的严重改变，这让人想起Alport综合征，并包括大量的基底膜增厚和分裂。这些损害与GBM成分的表达增加有关。足细胞异常、足突消失和足细胞丢失似乎是基底膜损伤的结果。综上所述，CD151除了在整合素介导的黏附增强中发挥作用外，似乎还参与了GBM结构的建立、成熟和/或维持。
Alterations in CD151 have been associated with primary glomerular disease in both humans and mice, implicating CD151 as a key component of the glomerular filtration barrier. CD151 belongs to the tetraspanin family and associates with cell-matrix adhesion complexes such as alpha 3 beta 1-integrin. Here we show that Cd151-deficient mice develop severe kidney disease on an FVB background but are healthy on a B6 background. providing a new and unique tool for the identification of genes that modulate the onset of proteinuria. To better understand the function of CD151 in the kidney, we studied it expression pattern and characterized early ultrastructural defects in Cd151-null kidneys. CD151 is expressed in podocytes of the mouse kidney and co-localizes with alpha 3-integrin at the base of podocyte foot processes, at the site of anchorage to the glomerular basement membrane (GBM). Interestingly, the first ultra-structural lesions seen at the onset of proteinuria in Cd151-null kidneys were severe alterations of the GBM, reminiscent of Alport syndrome and consisting of massive thickening and splitting of the GBM. These lesions are associated with increased expression of GBM components. Podocyte abnormalities, effacement of foot processes, and podocyte loss appear to occur consequently to the GBM damage. In conclusion, CD151 appears to he involved in the establishment, maturation, and/or maintenance of the GBM structure in addition to its role in integrin-mediated adhesion strengthening.