title: Dissociation of NEPH1 from nephrin is involved in development of a rat model of focal segmental glomerulosclerosis.
abstract: Focal segmental glomerulosclerosis (FSGS) is a disease showing severe proteinuria, and the disease progresses to end-stage kidney failure in many cases. However, the pathogenic mechanism of FSGS is not well understood. The slit diaphragm (SD), which bridges the neighboring foot processes of glomerular epithelial cells, is understood to function as a barrier of the glomerular capillary wall. To investigate the role of SD dysfunction in the development of FSGS, we analyzed the expression of SD-associated molecules in rat adriamycin-induced nephropathy, a mimic of FSGS. The staining of the SD molecules nephrin, podocin, and NEPH1 had already shifted to a discontinuous dotlike pattern at the initiation phase of the disease, when neither proteinuria nor any morphological alterations were detected yet. The alteration of NEPH1 expression was the most evident among the molecules examined, and NEPH1 was dissociated from nephrin at the initiation phase. On day 28, when severe proteinuria was detected and sclerotic changes were already observed, alteration of the expressions of nephrin, podocin, and NEPH1 worsened, but no alteration in the expression of other SD-associated molecules or other podocyte molecules was detected. It is postulated that the dissociation of NEPH1 from nephrin initiates proteinuria and that the SD alteration restricted in these molecules plays a critical role in the development of sclerotic changes in FSGS.
authors: Department of Cell Biology, Institute of Nephrology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Niigata, 951-8510, Japan.
authors: Yasuhiro
authors: Y
authors: Otaki
authors: Naoko
authors: N
authors: Miyauchi
authors: Mutsumi
authors: M
authors: Higa
authors: Akira
authors: A
authors: Takada
authors: Takeshi
authors: T
authors: Kuroda
authors: Fumitake
authors: F
authors: Gejyo
authors: Fujio
authors: F
authors: Shimizu
authors: Hiroshi
authors: H
authors: Kawachi
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000906:Antibodies / Q000276:immunology; D015153:Blotting, Western; D003001:Cloning, Molecular; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D004317:Doxorubicin; D004622:Embryo, Mammalian / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D005923:Glomerulosclerosis, Focal Segmental / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism*; D016023:Integrins / Q000235:genetics / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D007678:Kidney Glomerulus / Q000196:embryology / Q000378:metabolism / Q000473:pathology; D007684:Kidney Tubules / Q000378:metabolism / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D050199:Podocytes / Q000378:metabolism; D011485:Protein Binding; D011507:Proteinuria / Q000652:urine; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012795:Sialoglycoproteins / Q000235:genetics / Q000378:metabolism; D062826:Zonula Occludens-1 Protein
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000906:Antibodies; C114545:CD2-associated protein; D003598:Cytoskeletal Proteins; D016023:Integrins; D047908:Intracellular Signaling Peptides and Proteins; C486607:Kirrel1 protein, rat; D008565:Membrane Proteins; C407223:NPHS2 protein; D010750:Phosphoproteins; D012795:Sialoglycoproteins; C569044:Tjp1 protein, rat; D062826:Zonula Occludens-1 Protein; C113267:nephrin; C001643:podocalyxin; D004317:Doxorubicin