title: Translocation of dendrin to the podocyte nucleus in acute glomerular injury in patients with IgA nephropathy.
abstract: BACKGROUND
  It has been reported that podocytopenia has been occurring with increasing disease severity in patients with IgA nephropathy (IgAN). Dendrin is localized at the slit diaphragm (SD) in podocytes. We showed that dendrin translocates to the nucleus of injured podocytes in experimental nephritis and the nuclear dendrin promotes podocyte apoptosis. It is still unknown whether dendrin translocates from the SD to podocyte nucleus in IgAN. We investigated the presence of nuclear dendrin in patients with IgAN and the association between the translocated dendrin to the podocyte nucleus and disease activity.
  
  
  METHODS
  Fourteen adult patients with IgAN were enrolled. The pathological parameters were analyzed. Immunostaining of renal biopsy specimens and urinary sediments from IgAN or minimal change nephrotic syndrome (MCNS) as the control was performed.
  
  
  RESULTS
  A positive correlation was observed between an acute extracapillary change and the number of dendrin-positive nuclei. The location of dendrin in the nuclei was found in urinary podocytes of IgAN. The number of dendrin-positive nuclei in urinary podocytes of IgAN was significantly higher than that of MCNS. Urinary podocytes, which expressed the apoptosis marker annexin V, were also detected in IgAN. The translocation of dendrin to the podocyte nucleus as well as strong cathepsin L staining were detected in the glomeruli of IgAN.
  
  
  CONCLUSIONS
  An increasing number of dendrin-positive nuclei in the glomeruli suggest acute glomerular injury in IgAN. Apoptotic podocytes were detectable in the urine of IgAN. It appears that the translocation of dendrin to the podocyte nuclei enhances podocyte apoptosis in acute glomerular injury and leads to podocytopenia in patients with IgAN.
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Juntendo University Faculty of Medicine, Tokyo, Japan.
authors.forename: Fumiko
authors.initials: F
authors.lastname: Kodama
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Asanuma
authors.forename: Miyuki
authors.initials: M
authors.lastname: Takagi
authors.forename: Teruo
authors.initials: T
authors.lastname: Hidaka
authors.forename: Etsuko
authors.initials: E
authors.lastname: Asanuma
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Fukuda
authors.forename: Takuto
authors.initials: T
authors.lastname: Seki
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Takeda
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Hosoe-Nagai
authors.forename: Rin
authors.initials: R
authors.lastname: Asao
authors.forename: Satoshi
authors.initials: S
authors.lastname: Horikoshi
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Tomino
mesh_terms: D058186:Acute Kidney Injury / Q000175:diagnosis* / Q000209:etiology / Q000378:metabolism; D000328:Adult; D017209:Apoptosis; D015415:Biomarkers / Q000652:urine*; D002467:Cell Nucleus / Q000378:metabolism*; D005260:Female; D005455:Fluorescent Antibody Technique; D005919:Glomerular Filtration Rate; D005922:Glomerulonephritis, IGA / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007678:Kidney Glomerulus / Q000473:pathology*; D008297:Male; D009419:Nerve Tissue Proteins / Q000652:urine*; D050199:Podocytes / Q000378:metabolism / Q000473:pathology*; D021381:Protein Transport; D055815:Young Adult
chemical_list: D015415:Biomarkers; D009419:Nerve Tissue Proteins; C104328:dendrin
keywords: IgA nephropathy; dendrin; glomerulosclerosis; podocyte