title: Temporal and spatial expression of podocyte-associated molecules are accompanied by proteinuria in IgA nephropathy rat model.
abstract: We used a rat model to assess the role of nephrin, podocin, and desmin in the pathogenesis of IgA nephropathy (IgAN). A rat IgAN model was established by administration of BSA, CCl(4), and lipopolysaccharide (LPS) and compared with healthy control rats. Urinary protein, urine red blood cells, and biochemical parameters were measured for 12 weeks. Renal morphology and ultrastructure were examined by light and electron microscopy. Immunofluorescence was used to assess IgA deposition in the glomeruli and to measure expression of nephrin, podocin, and desmin. Real-time quantitative PCR was used to measure expression of nephrin, podocin, and desmin mRNAs. IgAN rats developed proteinuria at week-6 and this worsened over time. Pathological changes were evident under light microscopy at week-8 and under electron microscopy at week-4. Immunofluorescence analysis showed deposition of IgA in the kidneys of IgAN rats, but not control rats. IgAN rats had increased expression of glomerular podocin, nephrin, and desmin mRNAs and proteins at week-4. The expression of nephrin, podocin and desmin proteins and the expression of podocin and desmin mRNAs preceded the increase in urinary protein. Taken together, our study of a rat model of IgAN indicates that changes in the expression and distribution of nephrin, podocin, and desmin precede and may cause foot process fusion and proteinuria.
authors.affiliation: Department of Pediatrics, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. xyjiang-3208@163.com
authors.forename: H
authors.initials: H
authors.lastname: Lu
authors.forename: L L
authors.initials: LL
authors.lastname: Chen
authors.forename: X Y
authors.initials: XY
authors.lastname: Jiang
authors.forename: Y
authors.initials: Y
authors.lastname: Mo
authors.forename: Y H
authors.initials: YH
authors.lastname: Ling
authors.forename: L Z
authors.initials: LZ
authors.lastname: Sun
mesh_terms: D000818:Animals; D003893:Desmin / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D018450:Disease Progression; D005455:Fluorescent Antibody Technique; D005922:Glomerulonephritis, IGA / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology / Q000652:urine; D006417:Hematuria / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D046529:Microscopy, Electron, Transmission; D050199:Podocytes / Q000378:metabolism* / Q000648:ultrastructure; D011507:Proteinuria / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology / Q000652:urine; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
chemical_list: D003893:Desmin; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C407223:NPHS2 protein; D012333:RNA, Messenger; C113267:nephrin