title: Indoxyl sulfate induces epithelial-to-mesenchymal transition in rat kidneys and human proximal tubular cells.
abstract: OBJECTIVE
  Indoxyl sulfate (IS) is a uremic toxin that accelerates the progression of chronic kidney disease (CKD). This study aimed to determine if IS induces epithelial-to-mesenchymal transition (EMT) in the kidneys of hypertensive rats and human proximal tubular cells (HK-2).
  
  
  METHODS
  EMT was evaluated by immunohistochemistry, reverse transcription-polymerase chain reaction and immunoblotting of the epithelial markers E-cadherin and zonula occludens-1 (ZO-1), and the mesenchymal marker α-smooth muscle actin (α-SMA). Rat groups consisted of (1) Dahl salt-resistant normotensive rats (DN), (2) Dahl salt-resistant normotensive IS-administered rats (DN+IS), (3) Dahl salt-sensitive hypertensive rats (DH), and (4) Dahl salt-sensitive hypertensive IS-administered rats (DH+IS). HK-2 cells were incubated with or without IS.
  
  
  RESULTS
  In kidneys, DH rats showed reduced expression of E-cadherin and ZO-1, and enhanced expression of α-SMA compared with DN rats. DN+IS and DH+IS rats showed reduced expression of E-cadherin and ZO-1, and enhanced expression of α-SMA compared with DN and DH rats, respectively. DH+IS and DH rats showed increased Masson's trichrome-positive fibrosis areas compared with DH and DN, respectively. IS-treated HK-2 cells showed reduced expression of E-cadherin and ZO-1, and enhanced expression of α-SMA.
  
  
  CONCLUSIONS
  IS induces EMT in the kidneys of hypertensive rats and in human proximal tubular cells.
authors.affiliation: Department of Advanced Medicine for Uremia, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku,Nagoya, Japan.
authors.forename: Dilinaer
authors.initials: D
authors.lastname: Bolati
authors.forename: Hidehisa
authors.initials: H
authors.lastname: Shimizu
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Higashiyama
authors.forename: Fuyuhiko
authors.initials: F
authors.lastname: Nishijima
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Niwa
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000473:pathology; D007150:Immunohistochemistry / Q000379:methods; D007200:Indican / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D007687:Kidney Tubules, Proximal / Q000166:cytology*; D008565:Membrane Proteins / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D051381:Rats; D020303:Rats, Inbred Dahl; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D015398:Signal Transduction; D013997:Time Factors; D062826:Zonula Occludens-1 Protein
chemical_list: D000199:Actins; D008565:Membrane Proteins; D010750:Phosphoproteins; C569042:TJP1 protein, human; C569044:Tjp1 protein, rat; D062826:Zonula Occludens-1 Protein; D007200:Indican