Apical Cell Membranes Are Shed into Urine from Injured Podocytes
Autor: | Masanori Hara, Itaru Kihara, Tadahiro Kajita, Toshio Yanagihara, Kazuhiro Higashi, Kotarou Fujimoto |
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Rok vydání: | 2005 |
Předmět: |
Adult
Male Pathology medicine.medical_specialty DNA Complementary Nephrotic Syndrome Adolescent Sialoglycoproteins Blotting Western Kidney Glomerulus Enzyme-Linked Immunosorbent Assay Apical cell Urine Biology Kidney Function Tests Immunofluorescence Sensitivity and Specificity Severity of Illness Index Statistics Nonparametric Podocyte chemistry.chemical_compound Glomerulonephritis Reference Values medicine Humans Child Probability Urine cytology Kidney medicine.diagnostic_test Cell Membrane General Medicine Prognosis medicine.disease Proteinuria medicine.anatomical_structure Podocalyxin chemistry Nephrology Case-Control Studies Child Preschool Female Nephritis Biomarkers |
Zdroj: | Journal of the American Society of Nephrology. 16:408-416 |
ISSN: | 1046-6673 |
Popis: | Previously it was shown that urine from patients with nephritis contains podocytes and their fragments (podocalyxin [PCX]-positive granular structures [PPGS]), reflecting the degree of podocyte injury. The present study was designed to trace PPGS to their origin. Urine samples and renal biopsy specimens from 53 children with nephrotic syndrome and nephritis were examined immunohistochemically. Immunofluorescence studies of kidney sections using an anti-PCX antibody demonstrated that PPGS originated from the glomerulus and flowed into the tubular lumen. Electron microscopic examination revealed that PPGS originated from microvillous or vesicle-like structures on injured podocytes in the glomerulus. For examining the origin of the PPGS, apical, slit-diaphragmatic, and basal portions of the podocytes were specifically stained, revealing that PPGS are composed primarily of apical podocyte membranes. Several newly developed antibodies that are reactive with various segments of the PCX molecule were used to analyze more detailed membrane structures, and it was found that PPGS contained intact PCX molecules, indicating that cell membrane structures are excreted in urine. The quantification of PCX content and podocyte numbers revealed that urinary sediment PCX (u-sed-PCX) content per urinary podocyte was much higher than PCX content per podocyte from isolated glomeruli of normal controls, suggesting that u-sed-PCX are derived from sources other than just the cell debris of detached podocytes. Analysis of the correlation between u-sed-PCX and renal histology revealed that the presence of PPGS reflects acute glomerular injury. In conclusion, podocyte apical cell membranes are shed into the urine from injured podocytes, indicating a previously unrecognized manifestation of podocyte injury. |
Databáze: | OpenAIRE |
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