title: Expression of the transcriptional regulator snail1 in kidney transplants displaying epithelial-to-mesenchymal transition features.
abstract: BACKGROUND
  The epithelial response to injury is stereotypical and reminiscent of epithelial-to-mesenchymal transitions (EMTs), such as those observed during embryogenesis and tumour metastasis. In the context of solid organ transplantation, EMT-like features are often acquired by epithelial cells and are predictive of graft fibrosis. Here, we studied the possible involvement of several major transcriptional regulators, including snail1, phospho-Smad 2/3 and zeb1, in EMT induction in human renal grafts.
  
  
  METHODS
  We used immunohistochemistry to detect the presence of these EMT transcriptional regulators along with that of two validated EMT markers (intra-cytoplasmic translocation of β-catenin, de novo expression of vimentin), in 103 renal graft biopsy samples taken for routine surveillance or for a clinical indication.
  
  
  RESULTS
  We observed the nuclear accumulation of snail1 and phospho-smad2/3 in tubular cells displaying EMT. The level of snail1 was significantly correlated with the scores of EMT markers (β-catenin: ρ = 0.94, P < 0.0001; vimentin: ρ = 0.93, P < 0.0001) and with deteriorated graft function and proteinuria at the time of biopsy. Furthermore, intense staining for both snail1 and vimentin in tubular cells (≥10% of tubules) was predictive of graft dysfunction 21 months post-biopsy, independently of the other known risk factor for long-term graft dysfunction. In contrast, in both normal and diseased graft, zeb1 expression was detected exclusively in the endothelial cells of glomeruli and peritubular capillaries.
  
  
  CONCLUSIONS
  This study suggests that snail1 is closely related to the fibrogenic, EMT-like response of the tubular epithelium in human renal grafts and predictive of graft function loss.
authors.affiliation: INSERM U702, Hôpital Tenon, Paris, France Département de Santé Publique, APHP, Hôpital Tenon, Paris, France.
authors.forename: Yi-Chun
authors.initials: YC
authors.lastname: Xu-Dubois
authors.affiliation: INSERM U702, Hôpital Tenon, Paris, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Galichon
authors.affiliation: Anatomo-Pathologie, APHP, Hôpital Tenon, Paris, France Université Pierre et Marie Curie, Paris 6, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Brocheriou
authors.affiliation: INSERM U702, Hôpital Tenon, Paris, France.
authors.forename: Edith
authors.initials: E
authors.lastname: Baugey
authors.affiliation: IFR65, Imagerie cellulaire, Université Pierre et Marie Curie, Paris 6, France.
authors.forename: Romain
authors.initials: R
authors.lastname: Morichon
authors.affiliation: INSERM U702, Hôpital Tenon, Paris, France.
authors.forename: Chantal
authors.initials: C
authors.lastname: Jouanneau
authors.affiliation: Urgences Néphrologiques et Transplantation Rénale, APHP, Hôpital Tenon, Paris, France.
authors.forename: Nacera
authors.initials: N
authors.lastname: Ouali
authors.affiliation: INSERM U702, Hôpital Tenon, Paris, France Anatomo-Pathologie, APHP, Hôpital Tenon, Paris, France Urgences Néphrologiques et Transplantation Rénale, APHP, Hôpital Tenon, Paris, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Rondeau
authors.affiliation: INSERM U702, Hôpital Tenon, Paris, France Anatomo-Pathologie, APHP, Hôpital Tenon, Paris, France Urgences Néphrologiques et Transplantation Rénale, APHP, Hôpital Tenon, Paris, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Hertig
mesh_terms: D001706:Biopsy; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D005355:Fibrosis / Q000378:metabolism / Q000473:pathology; D006084:Graft Rejection / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007676:Kidney Failure, Chronic / Q000601:surgery; D016030:Kidney Transplantation; D007684:Kidney Tubules / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D051899:Smad2 Protein / Q000096:biosynthesis*
chemical_list: C497782:SMAD2 protein, human; D051899:Smad2 Protein
keywords: EMT; early fibrotic markers; kidney; transcriptional factors; transplantation