The role of caveolae on albumin passage through glomerular endothelial and epithelial cells: The new etiology of urinary albumin excretion
The role of caveolae on albumin passage through glomerular endothelial and epithelial cells: The new etiology of urinary albumin excretion
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小窝对白蛋白通过肾小球内皮和上皮细胞的作用：尿白蛋白排泄的新病因
DOI：
10.1159/000486929
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发表时间：
2018
影响因子：
--
通讯作者：
Kosaku Nitta
中科院分区：
文献类型：
--
作者：
Takahito Moriyama;Kazunori Karasawa;Kosaku Nitta
在传统的蛋白尿理论中，少量的白蛋白通过肾小球内皮细胞的窗口，然后通过肾小球上皮细胞足突间隙的狭缝膜。在新的理论中，大量的白蛋白通过肾小球毛细血管，并被小管上皮细胞上的巨噬蛋白和立方蛋白受体所吸收。尿白蛋白排泄的这些病因仍然存在争议，白蛋白通过肾小球毛细血管三层（肾小球内皮细胞、基底膜和上皮细胞）的细节从未完全阐明。基础研究的最新进展表明，位于肾小球内皮细胞和上皮细胞表面的细胞内陷，在白蛋白的内吞、胞吞和胞吐中起关键作用。白蛋白通过小泡进入肾小球内皮细胞和上皮细胞；在肾小球内皮细胞中，随后的白蛋白胞吞作用不依赖于肌动蛋白或微管，但在肾小球上皮细胞中则依赖于肌动蛋白。肾小球内皮细胞中白蛋白的胞吐通过早期核内体发生，该过程绕过其他核内体相关细胞器。相反，肾小球上皮细胞中白蛋白的胞外分泌通过早期内体发生，这一过程导致一些白蛋白颗粒的溶酶体降解。这种依赖于小泡的途径可能为白蛋白通过肾小球内皮细胞和上皮细胞提供了一种新的病理生理学，导致尿白蛋白排泄的新病因学，将传统的和新的白蛋白尿理论联系起来。©2018 S. Karger AG，巴塞尔
BackgroundIn the traditional theory of albuminuria, small amounts of albumin pass through the fenestrae in glomerular endothelial cells, then through the slit membrane in the gaps between foot processes of glomerular epithelial cells. In the novel theory, large amounts of albumin pass through glomerular capillaries and are taken up by megalin and cubilin receptors on tubular epithelial cells. These etiologies of urinary albumin excretion are still controversial, and the details of albumin passage through the three layers of glomerular capillaries (glomerular endothelial cells, basement membrane, and epithelial cells) have never been entirely elucidated.SummaryRecent advances in basic research have shown that caveolae, which are cell invaginations located on the surface of both glomerular endothelial and epithelial cells, play pivotal roles in the endocytosis, transcytosis, and exocytosis of albumin. Albumin enters into glomerular endothelial and epithelial cells through caveolae; subsequent transcytosis of albumin is not actin-or microtubuledependent in glomerular endothelial cells, but is actin-dependent in glomerular epithelial cells. Exocytosis of albumin in glomerular endothelial cells occurs via early endosomes through a process that bypasses other endosome-associated organelles. In contrast, exocytosis of albumin in glomerular epithelial cells occurs via early endosomes through a process that results in lysosomal degradation of some albumin particles.Key MessagesThis caveolae-dependent pathway may provide a new pathophysiology for albumin passage through glomerular endothelial and epithelial cells, leading to a new etiology for urinary albumin excretion that connects both traditional and novel theories of albuminuria.© 2018 S. Karger AG, Basel