title: Effect of 5/6 nephrectomized rat serum on epithelial-to-mesenchymal transition in vitro.
abstract: OBJECTIVE
  To investigate whether the 5/6 nephrectomized (5/6Nx) rats' 12-week serum could lead to tubular epithelial-to-mesenchymal transition (EMT) and its molecular mechanism, so as to probe the potential stimulation from circulation in chronic progressive kidney disease.
  
  
  METHODS
  A total of 24 Sprague Dawley (SD) rats were randomly divided into two groups: sham operation group (sham group) and 5/6Nx group. Rats were killed 12 weeks after surgery to obtain 5/6Nx rats' 12-week serum. Then we detected the expression of E-cadherin in renal tubular epithelial cells of the remaining kidney and we investigated whether the 12th week serum of 5/6Nx rats could cause HK-2 (human kidney proximal tubular cell line) cells to transdifferentiate into fibroblasts.
  
  
  RESULTS
  Our data confirmed that E-cadherin expression decreased significantly in the remaining kidney at 12 weeks, and the 5/6Nx rats' 12-week serum could suppress E-cadherin protein and mRNA expression (p < 0.05). We also found that the 5/6Nx rats' 12-week serum could upregulate ZEB1, β-catenin, and wnt3 protein expression (p < 0.05).
  
  
  CONCLUSIONS
  Our results demonstrated that the 5/6Nx rats' 12-week serum could suppress the expression of E-cadherin in HK-2 cells. It was partially through modulating the increase of ZEB1. The loss of E-cadherin could lead β-catenin to localize to the cytoplasm and nucleus, and feed into the Wnt signaling pathway. It means that the pathogenic serum in chronic kidney disease (CKD) plays an important role in the loss of renal function and turns to be a new avenue of research with potential clinical implications.
authors.affiliation: Department of Nephrology, Chinese PLA General Hospital, Beijing, People's Republic of China.
authors.forename: Zhaoyu
authors.initials: Z
authors.lastname: Lu
authors.forename: Yuansheng
authors.initials: Y
authors.lastname: Xie
authors.forename: Xusheng
authors.initials: X
authors.lastname: Liu
authors.forename: Shaoyuan
authors.initials: S
authors.lastname: Cui
authors.forename: Yuchi
authors.initials: Y
authors.lastname: Wu
authors.forename: Cun
authors.initials: C
authors.lastname: Cai
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Xiangmei
authors.initials: X
authors.lastname: Chen
mesh_terms: D000818:Animals; D015153:Blotting, Western; D015820:Cadherins / Q000096:biosynthesis; D054338:Cell Transdifferentiation / Q000502:physiology*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004848:Epithelium / Q000378:metabolism* / Q000473:pathology; D005355:Fibrosis; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D008297:Male; D008648:Mesoderm / Q000378:metabolism* / Q000473:pathology; D008856:Microscopy, Fluorescence; D009392:Nephrectomy / Q000009:adverse effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044967:Serum; D015398:Signal Transduction; D060508:Wnt3 Protein / Q000096:biosynthesis; D051176:beta Catenin / Q000096:biosynthesis
chemical_list: D015820:Cadherins; D060508:Wnt3 Protein; D051176:beta Catenin