Mice lacking core 1-derived O-glycan in podocytes develop transient proteinuria, resulting in focal segmental glomerulosclerosis
Mice lacking core 1-derived O-glycan in podocytes develop transient proteinuria, resulting in focal segmental glomerulosclerosis
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DOI：
10.1016/j.bbrc.2020.01.033
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发表时间：
2020-03-19
影响因子：
3.1
通讯作者：
Takahashi, Satoru
中科院分区：
文献类型：
--
作者：
Fuseya, Sayaka;Suzuki, Riku;Takahashi, Satoru
肾小球滤过屏障由足细胞、肾小球基底膜和内皮细胞组成。这些结构的破坏导致多种肾小球损伤，如局灶节段性肾小球硬化（FSGS）。足细胞根尖膜表面被带负电荷的唾液酸覆盖在核心1-衍生黏液型o -聚糖上。在这里，我们的目的是利用缺乏足细胞特异性核心1衍生o -聚糖（iPod-Cos）的成年小鼠来研究核心1衍生o -聚糖在足细胞中的生理作用。iPod-Cos小鼠表现出早期和短暂性蛋白尿伴足突消退，并出现典型的fsgs样疾病症状。为了确定fgs样表型的关键分子，我们重点研究了podocalyxin和podoplanin，它们具有粘蛋白型o -聚糖。podocalyxin在iPod-Cos肾小球中的表达和定位没有变化。此外，western blot分析显示，与对照肾小球相比，iPod-Cos小鼠离体肾小球中完整足alyxin水平显著降低，而iPod-Cos肾小球中加工形式水平较高。相反，iPod-Cos小鼠的podoplanin mRNA和蛋白水平低于对照小鼠。这些结果表明，足细胞上的核心1衍生的o -聚糖是正常肾小球滤过所必需的，并可能有助于足alyxin和足planin的稳定表达。(C) 2020爱思唯尔公司版权所有。
The glomerular filtration barrier is composed of podocytes, glomerular basement membrane, and endothelial cells. Disruption of these structures causes several glomerular injuries, such as focal segmental glomerulosclerosis (FSGS). The surface of podocyte apical membranes is coated by negatively charged sialic acids on core 1-derived mucin-type O-glycans. Here, we aimed to investigate the physiological role of core 1-derived O-glycans in the podocytes using adult mice lacking podocyte-specific core 1-derived O-glycans (iPod-Cos). iPod-Cos mice exhibited early and transient proteinuria with foot process effacements and developed typical FSGS-like disease symptoms. To identify the key molecules responsible for the FSGS-like phenotype, we focused on podocalyxin and podoplanin, which possess mucin-type O-glycans. Expression and localization of podocalyxin did not change in iPod-Cos glomeruli. Besides, western blot analysis revealed significantly lower levels of intact podocalyxin in isolated glomeruli of iPod-Cos mice, and high levels of processed forms in iPod-Cos glomeruli, as compared to that in control glomeruli. Conversely, podoplanin mRNA, and protein levels were lower in iPod-Cos mice than in control mice. These results demonstrated that core 1-derived O-glycan on podocytes is required for normal glomerular filtration and may contribute to the stable expression of podocalyxin and podoplanin. (C) 2020 Elsevier Inc. All rights reserved.