title: Reduced INF2 expression in nephrotic syndrome is possibly related to clinical severity of steroid resistance in children.
abstract: OBJECTIVE
  Mutations of the inverted formin 2 gene (INF2), which encodes a member of the formin family, cause autosomal dominant focal segmental glomerulosclerosis (FSGS) and Charcot-Marie-Tooth (CMT) disease-associated FSGS. However, their role in idiopathic FSGS remains unclear. This study investigated INF2 localization in the normal adult kidney and its expression in children with idiopathic nephrotic syndrome.
  
  
  METHODS
  We generated a rabbit polyclonal antibody against the conjugated peptide from human INF2 and studied the glomerular expression of INF2 and synaptopodin using normal human adult kidney tissues and tissues from children with glomerular diseases such as minimal change disease (MCD), FSGS, IgA nephropathy (IgAN), non-IgA mesangial proliferative glomerulonephritis (non-IgAN), and Henoch-Schönlein purpura nephritis (HSPN).
  
  
  RESULTS
  The anti-INF2 antibody detected an approximately 140-kD fragment isolated from adult mature glomeruli by western blotting. Immunohistochemically, INF2 was detected in podocytes and renal arteries. Among 56 patients, INF2 in glomeruli was expressed at a similar level in patients with MCD, IgAN, non-IgAN, or HSPN and controls. In FSGS patients, INF2 expression in glomeruli was either decreased or absent. There was a relationship between decreased INF2 expression and the clinical severity of steroid resistant nephrotic syndrome (SRNS).
  
  
  CONCLUSIONS
  We propose that examination of INF2 expression may help to differentiate MCD from FSGS and evaluate the clinical severity of SRNS in children.
authors.affiliation: Department of Pediatrics, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tamura
authors.affiliation: Department of Pediatrics, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Nakazato
authors.affiliation: Department of Pediatrics, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Shohei
authors.initials: S
authors.lastname: Kuraoka
authors.affiliation: Department of Pediatrics, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Yoneda
authors.affiliation: Department of Urology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Takahashi
authors.affiliation: Department of Pediatrics, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Fumio
authors.initials: F
authors.lastname: Endo
mesh_terms: D000293:Adolescent; D000367:Age Factors; D015415:Biomarkers / Q000032:analysis; D001706:Biopsy; D015153:Blotting, Western; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003937:Diagnosis, Differential; D015536:Down-Regulation; D005260:Female; D000080865:Formins; D005923:Glomerulosclerosis, Focal Segmental / Q000175:diagnosis / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007678:Kidney Glomerulus / Q000737:chemistry* / Q000473:pathology; D008297:Male; D008840:Microfilament Proteins / Q000032:analysis*; D009402:Nephrosis, Lipoid / Q000175:diagnosis / Q000378:metabolism*; D009404:Nephrotic Syndrome / Q000151:congenital* / Q000175:diagnosis / Q000378:metabolism; D011237:Predictive Value of Tests; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers; D000080865:Formins; C546959:INF2 protein, human; D008840:Microfilament Proteins; C503967:SYNPO protein, human
keywords: focal segmental glomerulosclerosis; inverted formin 2 gene; nephrotic syndrome; synaptopodin