The slit diaphragm bridging the neighboring foot pro-cesses functions as a fnal barrier of glomerular capil-lary wall for preventing the leak of plasma proteins into primary urine. It is now accepted that the dysfunct...The slit diaphragm bridging the neighboring foot pro-cesses functions as a fnal barrier of glomerular capil-lary wall for preventing the leak of plasma proteins into primary urine. It is now accepted that the dysfunction of the sit diaphragm contributes to the development of proteinuria in several glomerular diseases. Neph-rin, a gene product of NPHS1, a gene for a congenital nephrotic syndrome of Finnish type, constitutes an ex-tracellular domain of the slit diaphragm. Podocin was identified as a gene product of NPHS2 , a gene for a familial steroid-resistant nephrotic syndrome of French. Podocin binds the cytoplasmic domain of nephrin. After then, CD2 associated protein, NEPH1 and transient re-ceptor potential-6 were also found as crucial molecules of the slit diaphragm. In order to explore other novel molecules contributing to the development of protein-uria, we performed a subtraction hybridization assay with a normal rat glomerular RNA and a glomerular RNA of rats with a puromycin aminonucleoside ne-phropathy, a mimic of a human minimal change type nephrotic syndrome. Then we have found that synaptic vesicle protein 2B, ephrin-B1 and neurexin were already downregulated at the early stage of puromycin aminonucleoside nephropathy, and that these molecules were localized close to nephrin. It is conceivable that these molecules are the slit diaphragm associated molecules, which participate in the regulation of the barrier func-tion. These molecules could be targets to establish a novel therapy for nephrotic syndrome.展开更多
文摘The slit diaphragm bridging the neighboring foot pro-cesses functions as a fnal barrier of glomerular capil-lary wall for preventing the leak of plasma proteins into primary urine. It is now accepted that the dysfunction of the sit diaphragm contributes to the development of proteinuria in several glomerular diseases. Neph-rin, a gene product of NPHS1, a gene for a congenital nephrotic syndrome of Finnish type, constitutes an ex-tracellular domain of the slit diaphragm. Podocin was identified as a gene product of NPHS2 , a gene for a familial steroid-resistant nephrotic syndrome of French. Podocin binds the cytoplasmic domain of nephrin. After then, CD2 associated protein, NEPH1 and transient re-ceptor potential-6 were also found as crucial molecules of the slit diaphragm. In order to explore other novel molecules contributing to the development of protein-uria, we performed a subtraction hybridization assay with a normal rat glomerular RNA and a glomerular RNA of rats with a puromycin aminonucleoside ne-phropathy, a mimic of a human minimal change type nephrotic syndrome. Then we have found that synaptic vesicle protein 2B, ephrin-B1 and neurexin were already downregulated at the early stage of puromycin aminonucleoside nephropathy, and that these molecules were localized close to nephrin. It is conceivable that these molecules are the slit diaphragm associated molecules, which participate in the regulation of the barrier func-tion. These molecules could be targets to establish a novel therapy for nephrotic syndrome.
