RESUMEN
In addition to skeletal muscle and the nervous system, α-dystroglycan is found in the podocyte basal membrane, stabilizing these cells on the glomerular basement membrane. Fukutin, named after the gene responsible for Fukuyama-type congenital muscular dystrophy, is a putative glycosyltransferase required for the post-translational modification of α-dystroglycan. Chimeric mice targeted for both alleles of fukutin develop severe muscular dystrophy; however, these mice do not have proteinuria. Despite the lack of a functional renal defect, we evaluated glomerular structure and found minor abnormalities in the chimeric mice by light microscopy. Electron microscopy revealed flattening of podocyte foot processes, the number of which was significantly lower in the chimeric compared to wild-type mice. A monoclonal antibody against the laminin-binding carbohydrate residues of α-dystroglycan did not detect α-dystroglycan glycosylation in the glomeruli by immunoblotting or immunohistochemistry. In contrast, expression of the core α-dystroglycan protein was preserved. There was no statistical difference in dystroglycan mRNA expression or in the amount of nephrin and α3-integrin protein in the chimeric compared to the wild-type mice as judged by immunohistochemistry and real-time RT-PCR. Thus, our results indicate that appropriate glycosylation of α-dystroglycan has an important role in the maintenance of podocyte architecture.
Asunto(s)
Forma de la Célula , Distroglicanos/metabolismo , Podocitos/metabolismo , Procesamiento Proteico-Postraduccional , Síndrome de Walker-Warburg/metabolismo , Animales , Western Blotting , Modelos Animales de Enfermedad , Distroglicanos/genética , Glicosilación , Inmunohistoquímica , Integrina alfa3/metabolismo , Proteínas de la Membrana/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Microscopía Electrónica de Transmisión , Podocitos/patología , Reacción en Cadena de la Polimerasa , Proteínas/genética , Proteínas/metabolismo , ARN Mensajero/metabolismo , Transferasas , Síndrome de Walker-Warburg/genética , Síndrome de Walker-Warburg/patologíaRESUMEN
BACKGROUND/AIM: Plasma adiponectin may play a protective role in the pathogenesis of cardiovascular disease in hemodialysis (HD) patients. We examined the effect of plasma adiponectin levels on the prognosis of the HD patients. METHODS: 68 HD patients (male:female = 38:30) were subjected to plasma adiponectin measurement in 1998 and followed up over 8 years. RESULTS: Plasma adiponectin concentrations differed between male and female patients (9.3 vs. 15.7 microg/ml). The plasma adiponectin concentration as a whole was positively correlated with serum high-density lipoprotein cholesterol and negatively with serum creatinine and waist circumference. During an 8-year follow-up, the cardiac events occurred in 7 of 38 men and in 10 of 30 women. Cox's proportional hazard model analysis in a stepwise manner revealed that coronary heart disease (CHD) was associated with intact parathyroid hormone concentration, age, and the presence of diabetes in men whereas plasma adiponectin concentration was the most powerful single predictor in women. The impact of the plasma adiponectin concentration was strengthened by Kaplan-Meier survival analysis. In the group with a lower plasma adiponectin concentration, CHD events were significantly increased in men (p = 0.043) and in women (p = 0.007). CONCLUSION: Plasma adiponectin concentration may predict CHD outcomes in HD patients.