Loss of mucin-type O-glycans impairs the integrity of the glomerular filtration barrier in the mouse kidney
Loss of mucin-type O-glycans impairs the integrity of the glomerular filtration barrier in the mouse kidney
复制标题
粘蛋白型 O-聚糖的损失会损害小鼠肾脏中肾小球滤过屏障的完整性
DOI：
10.1074/jbc.m117.798512
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发表时间：
2017-10-06
影响因子：
4.8
通讯作者：
Xia, Lijun
中科院分区：
文献类型：
--
作者：
Song, Kai;Fu, Jianxin;Xia, Lijun
肾脏的过滤活动对于清除体内的毒素和废物至关重要。肾小球的血管内皮细胞有孔、扁平，并被足细胞包围，足细胞是支持肾小球内皮细胞的特殊细胞。粘蛋白型核心 1 衍生的 O-聚糖（O-聚糖）在肾小球毛细血管内皮细胞及其支持足细胞上高表达，但其生物学作用尚不清楚。核心 1 衍生的 O-聚糖的生物合成由糖基转移酶核心 1 β1,3-半乳糖基转移酶 (C1galt1) 催化。在这里，我们报告，具有 C1galt1 (iC1galt1−/−) 诱导缺失的新生或成年小鼠表现出自发性蛋白尿和快速进展的肾小球硬化。肾小球滤过屏障成分的超微结构分析表明，O-聚糖的丢失会导致足细胞足突的改变。进一步分析表明，O-聚糖对于足细胞足突相关糖蛋白足细胞萼蛋白的正常信号传导功能至关重要。我们的结果揭示了 O-糖基化在肾小球滤过屏障完整性中的新功能。
The kidney's filtration activity is essential for removing toxins and waste products from the body. The vascular endothelial cells of the glomerulus are fenestrated, flattened, and surrounded by podocytes, specialized cells that support glomerular endothelial cells. Mucin-type core 1–derived O-glycans (O-glycans) are highly expressed on both glomerular capillary endothelial cells and their supporting podocytes, but their biological role is unclear. Biosynthesis of core 1–derived O-glycans is catalyzed by the glycosyltransferase core 1 β1,3-galactosyltransferase (C1galt1). Here we report that neonatal or adult mice with inducible deletion of C1galt1 (iC1galt1−/−) exhibit spontaneous proteinuria and rapidly progressing glomerulosclerosis. Ultrastructural analysis of the glomerular filtration barrier components revealed that loss of O-glycans results in altered podocyte foot processes. Further analysis indicated that O-glycan is essential for the normal signaling function of podocalyxin, a podocyte foot process–associated glycoprotein. Our results reveal a new function of O-glycosylation in the integrity of the glomerular filtration barrier.