title: Intrauterine growth restriction leads to a dysregulation of Wilms' tumour supressor gene 1 (WT1) and to early podocyte alterations.
abstract: BACKGROUND
  Intrauterine growth restriction (IUGR) leads to low nephron number and higher incidence of renal disease. We hypothesized that IUGR induces early podocyte alterations based on a dysregulation of Wilms' tumour suppressor gene 1 (WT1), a key player of nephrogenesis and mediator of podocyte integrity.
  
  
  METHODS
  IUGR was induced in rats by maternal protein restriction during pregnancy. Kidneys were harvested from male offspring at Days 1 and 70 of life. qRT-PCR, immunohistochemistry and electron microscopy were performed in renal tissue. Albuminuria was assessed by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  At Day 70 of life, higher albuminuria and overt alterations of podocyte ultrastructure were detected in IUGR animals in spite of normal blood pressure. Moreover, we found increased glomerular immunoreactivity and expression of desmin, while synaptopodin and nephrin were decreased. Glomerular immunoreactivity and expression of WT1 were increased in IUGR animals at this time point with an altered expressional ratio of WT1 +KTS and -KTS isoforms. These changes of WT1 expression were already present at the time of birth.
  
  
  CONCLUSIONS
  IUGR results in early podocyte damage possibly due to a dysregulation of WT1. We suggest that an imbalance of WT1 isoforms to the disadvantage of -KTS affects nephrogenesis in IUGR rats and that persistent dysregulation of WT1 results in a reduced ability to maintain podocyte integrity, rendering IUGR rats more susceptible for renal disease.
authors.affiliation: Department of Pediatrics and Adolescent Medicine, University of Erlangen-Nuremberg, Erlangen, Germany. carlos.menendez-castro@ukerlangen.de
authors.forename: Carlos
authors.initials: C
authors.lastname: Menendez-Castro
authors.forename: Karl F
authors.initials: KF
authors.lastname: Hilgers
authors.forename: Kerstin
authors.initials: K
authors.lastname: Amann
authors.forename: Christoph
authors.initials: C
authors.lastname: Daniel
authors.forename: Nada
authors.initials: N
authors.lastname: Cordasic
authors.forename: Rainer
authors.initials: R
authors.lastname: Wachtveitl
authors.forename: Fabian
authors.initials: F
authors.lastname: Fahlbusch
authors.forename: Christian
authors.initials: C
authors.lastname: Plank
authors.forename: Jörg
authors.initials: J
authors.lastname: Dötsch
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Rascher
authors.forename: Andrea
authors.initials: A
authors.lastname: Hartner
mesh_terms: D000419:Albuminuria; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D001795:Blood Pressure Determination; D003893:Desmin / Q000235:genetics / Q000378:metabolism; D005260:Female; D005317:Fetal Growth Retardation / Q000378:metabolism / Q000473:pathology*; D005786:Gene Expression Regulation; D007124:Immunoenzyme Techniques; D007678:Kidney Glomerulus / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D009399:Nephrons / Q000378:metabolism / Q000473:pathology*; D050199:Podocytes / Q000378:metabolism / Q000473:pathology*; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D025721:WT1 Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D015415:Biomarkers; D003893:Desmin; D008565:Membrane Proteins; D008840:Microfilament Proteins; D012333:RNA, Messenger; C503969:Synpo protein, rat; D025721:WT1 Proteins; C113267:nephrin