title: Therapeutic target for nephrotic syndrome: Identification of novel slit diaphragm associated molecules.
abstract: The slit diaphragm bridging the neighboring foot processes functions as a final barrier of glomerular capillary 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. Nephrin, a gene product of NPHS1, a gene for a congenital nephrotic syndrome of Finnish type, constitutes an extracellular 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 receptor potential-6 were also found as crucial molecules of the slit diaphragm. In order to explore other novel molecules contributing to the development of proteinuria, we performed a subtraction hybridization assay with a normal rat glomerular RNA and a glomerular RNA of rats with a puromycin aminonucleoside nephropathy, 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 function. These molecules could be targets to establish a novel therapy for nephrotic syndrome.
authors.affiliation: Yoshiyasu Fukusumi, Naoko Miyauchi, Taeko Hashimoto, Akira Saito, Hiroshi Kawachi, Department of Cell Biology, Institute of Nephrology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan.
authors.forename: Yoshiyasu
authors.initials: Y
authors.lastname: Fukusumi
authors.affiliation: Yoshiyasu Fukusumi, Naoko Miyauchi, Taeko Hashimoto, Akira Saito, Hiroshi Kawachi, Department of Cell Biology, Institute of Nephrology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Miyauchi
authors.affiliation: Yoshiyasu Fukusumi, Naoko Miyauchi, Taeko Hashimoto, Akira Saito, Hiroshi Kawachi, Department of Cell Biology, Institute of Nephrology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan.
authors.forename: Taeko
authors.initials: T
authors.lastname: Hashimoto
authors.affiliation: Yoshiyasu Fukusumi, Naoko Miyauchi, Taeko Hashimoto, Akira Saito, Hiroshi Kawachi, Department of Cell Biology, Institute of Nephrology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Saito
authors.affiliation: Yoshiyasu Fukusumi, Naoko Miyauchi, Taeko Hashimoto, Akira Saito, Hiroshi Kawachi, Department of Cell Biology, Institute of Nephrology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawachi
keywords: Ephrin-B1; Neurexin; Podocyte; Slit diaphragm; Synaptic vesicle protein 2B