title: Emodin ameliorates high glucose induced-podocyte epithelial-mesenchymal transition in-vitro and in-vivo.
abstract: BACKGROUND
  Epithelial-to-mesenchymal transition (EMT) is a potential pathway leading to podocyte depletion and proteinuria in diabetic kidney disease (DKD). Here, we investigated the protective effects of Emodin (EMO) on high glucose (HG) induced-podocyte EMT in-vitro and in-vivo.
  
  
  METHODS
  Conditionally immortalized mouse podocytes were exposed to HG with 30 μg /ml of EMO and 1 μmol/ml of integrin-linked kinase (ILK) inhibitor QLT0267 for 24 h. Streptozotocin (STZ)-induced diabetic rats were treated with EMO at 20 mg· kg(-1)· d(-1) and QLT0267 at 10 mg· kg(-1)· w(-1) p.o., for 12 weeks. Albuminuria and blood glucose level were measured. Immunohistochemistry, immunofluorescence, western blotting and real-time PCR were used to detect expression of ILK, the epithelial marker of nephrin and the mesenchymal marker of desmin in-vitro and in-vivo.
  
  
  RESULTS
  HG increased podocyte ILK and desmin expression while decreased nephrin expression. However, EMO significantly inhibited ILK and desmin expression and partially restored nephrin expression in HG-stimulated podocytes. These in-vitro observations were further confirmed in-vivo. Treatment with EMO for 12 weeks attenuated albuminuria, renal histopathology and podocyte foot process effacement in diabetic rats. EMO also repressed renal ILK and desmin expression, preserved nephrin expression, as well as ameliorated albuminuria in STZ-induced diabetic rats.
  
  
  CONCLUSIONS
  EMO ameliorated glucose-induced EMT and subsequent podocyte dysfunction partly through ILK and desmin inhibition as well as nephrin upregulatiotion, which might provide a potential novel therapeutic option for DKD.
authors: Department of Medicine, Soochow University, Suzhou, PR China.
authors: Tingfang
authors: T
authors: Chen
authors: Li Yang
authors: LY
authors: Zheng
authors: Wenzhen
authors: W
authors: Xiao
authors: Dingkun
authors: D
authors: Gui
authors: Xiaoxia
authors: X
authors: Wang
authors: Niansong
authors: N
authors: Wang
mesh_terms: D000419:Albuminuria / Q000473:pathology / Q000652:urine; D000818:Animals; D001391:Azo Compounds / Q000494:pharmacology; D001786:Blood Glucose / Q000032:analysis; D003893:Desmin / Q000235:genetics / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D004642:Emodin / Q000494:pharmacology*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005947:Glucose / Q000633:toxicity; D007668:Kidney / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D050199:Podocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D020011:Protective Agents / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin / Q000633:toxicity; D015854:Up-Regulation / Q000187:drug effects; D000099200:Scaffold Protein ILK
chemical_list: D001391:Azo Compounds; D001786:Blood Glucose; D003893:Desmin; D004642:Emodin; D005947:Glucose; D008565:Membrane Proteins; D020011:Protective Agents; D017346:Protein Serine-Threonine Kinases; D011720:Pyrazoles; D013311:Streptozocin; D000099200:Scaffold Protein ILK; C552362:QLT 0267; C113267:nephrin