Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Renal-Electrolyte Division, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Kidney Int. 2019 Aug;96(2):270-272. doi: 10.1016/j.kint.2019.03.034.
The ability of proximal tubule cells to internalize filtered proteins over a broad concentration range is essential for maintaining a protein-free urine but also renders these cells uniquely susceptible to cytotoxic damage. Morace et al. find that knockout of globotriaosylceramide synthase, an enzyme required for production of Gb3 and other members of the globo series of glycosphingolipids, impairs endocytic uptake of filtered proteins and preserves kidney function in mouse models of acute kidney injury.
近端肾小管细胞能够在广泛的浓度范围内内化滤过的蛋白质,这对于维持无蛋白质尿液至关重要,但也使这些细胞容易受到细胞毒性损伤。Morace 等人发现,缺失糖鞘脂生物合成酶(globotriaosylceramide synthase),一种产生Gb3 和其他神经酰胺糖脂系列成员所必需的酶,会损害滤过蛋白质的内吞摄取,并在急性肾损伤的小鼠模型中保留肾功能。