1. Mice lacking core 1-derived O-glycan in podocytes develop transient proteinuria, resulting in focal segmental glomerulosclerosis
- Author
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Kunihiro Yamagata, Masato Kasahara, Toshiaki Usui, Satoru Takahashi, Hisashi Narimatsu, Sayaka Fuseya, Naoki Morito, Riku Suzuki, Takashi Kudo, Takashi Sato, Risa Okada, Kozue Hagiwara, and Hideki Yokoi
- Subjects
0301 basic medicine ,Kidney Glomerulus ,Biophysics ,urologic and male genital diseases ,Biochemistry ,Cell Line ,Podocyte ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Focal segmental glomerulosclerosis ,Western blot ,Polysaccharides ,medicine ,Animals ,Molecular Biology ,Glycoproteins ,Mice, Knockout ,medicine.diagnostic_test ,Glomerulosclerosis, Focal Segmental ,Podocytes ,urogenital system ,Chemistry ,Glomerular basement membrane ,Mucin-1 ,Cell Biology ,Galactosyltransferases ,medicine.disease ,Phenotype ,Cell biology ,Proteinuria ,030104 developmental biology ,medicine.anatomical_structure ,Podocalyxin ,Podoplanin ,030220 oncology & carcinogenesis ,Proteolysis ,Glomerular Filtration Barrier - Abstract
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.
- Published
- 2020