title: GSK-3β and vitamin D receptor are involved in β-catenin and snail signaling in high glucose-induced epithelial-mesenchymal transition of mouse podocytes.
abstract: BACKGROUND
  Epithelial-mesenchymal transition (EMT) is recognized to play an important role in diabetic nephropathy (DN).
  
  
  OBJECTIVE
  To analyze the roles of glycogen synthase kinase 3β (GSK-3β), β-catenin and Snail signaling in high glucose (HG)-induced mouse podocytes EMT.
  
  
  METHODS
  Differentiated podocytes were divided into: the normal glucose group (NG: glucose 5.6mM), the HG groups (12.5HG: 12.5mM; 25HG: 25mM; and 50HG: 50mM of glucose), and the osmotic control group (NG+M: glucose 5.6mM and mannitol 44.4mM). GSK-3β, β-catenin and Snail were assessed using semi-quantitative RT-PCR, western blot and immunofluorescence. β-catenin and Snail pathways were assessed after down-regulating GSK-3β expression using an inhibitor (LiCl) or a small-interfering RNA (siRNA).
  
  
  RESULTS
  HG increased GSK-3β, β-catenin and Snail expressions, and promoted EMT, as shown by decreased nephrin expression (epithelial marker), and increased α-SMA expression (mesenchymal marker). GSK-3β inhibitor and GSK-3β siRNA decreased β-catenin and Snail expressions, and reversed HG-induced EMT. Immunofluorescence showed that GSK-3β and β-catenin did not completely overlap; β-catenin was transferred to the nucleus in the 25HG group. VDR seems to be involved in HG-induced β-catenin nuclear translocation.
  
  
  CONCLUSIONS
  Down-regulating GSK-3β expression decreased β-catenin and Snail expression and reversed HG-induced podocytes EMT. Thus, modulating GSK-3β might be a target to slow or prevent DN. © 2014 S. Karger AG, Basel.
authors.affiliation: Department of Nephrology, the First Affiliated Hospital of Zhengzhou University, Henan, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Guo
authors.forename: Nannan
authors.initials: N
authors.lastname: Xia
authors.forename: Lili
authors.initials: L
authors.lastname: Yang
authors.forename: Sijie
authors.initials: S
authors.lastname: Zhou
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.forename: Yingjin
authors.initials: Y
authors.lastname: Qiao
authors.forename: Zhangsuo
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005947:Glucose / Q000494:pharmacology*; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D018021:Lithium Chloride / Q000494:pharmacology; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D050199:Podocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D018167:Receptors, Calcitriol / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D051176:beta Catenin / Q000378:metabolism
chemical_list: D000199:Actins; D008565:Membrane Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D018167:Receptors, Calcitriol; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; C544013:alpha-smooth muscle actin, mouse; D051176:beta Catenin; C113267:nephrin; D038362:Glycogen Synthase Kinase 3; D018021:Lithium Chloride; D005947:Glucose