title: Epithelial-to-mesenchymal transdifferentiation of renal tubular epithelial cell mediated by oxidative stress and intervention effect of probucol in diabetic nephropathy rats.
abstract: OBJECTIVE
  To elucidate the relationship of oxidative stress and specificity protein 1 (Sp1) in the process of epithelial-to-mesenchymal transdifferentiation (EMT) and also to investigate the molecular mechanism of protective effect of probucol on the pathogenesis of diabetic kidney disease (DKD).
  
  
  METHODS
  Thirty male Sprague-Dawley (SD) rats were randomly divided into control group, diabetic group, and diabetic group under probucol therapy (n = 10 per group). The biochemical indicators including 24-h urinary total protein (24-h UTP) excretion, blood glucose (BG), lipids [triglycerides (TGs), total cholesterol (TC)], serum creatinine (Scr), creatinine clearance rate (Ccr), kidney tissue malondialdehyde (MDA) level, and glutathione peroxidase (GSH-Px) activity were assessed in all groups. The renal pathological changes were evaluated by hematoxylin and eosin (HE) and Masson staining. The protein expression of Sp1, α-smooth muscle actin (α-SMA), and E-cadherin was also measured and analyzed by immunohistochemistry and Western blotting.
  
  
  RESULTS
  Compared with the control group, the BG, TC, Scr, 24-h UTP, and MDA level of renal tissue increased significantly and the Ccr reduced in the rats of diabetic group (all p < 0.01). The pathological scores and the expression of Sp1 and α-SMA in renal tissue were up-regulated (p < 0.01) and the expression of E-cadherin was down-regulated significantly in the diabetic animals (p < 0.01). In the diabetic animals treated with probucol, the renal injuries were alleviated (p < 0.01).
  
  
  CONCLUSIONS
  Oxidative stress may play an important role in the EMT process of tubular epithelial cells. Probucol could ameliorate renal disease progression in this model of diabetic nephropathy, which might be due to an antioxidant action, down-regulation of Sp1 protein expression, and inhibition of renal tubular EMT.
authors.affiliation: Institute of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, PR China. DuanSB528@hotmail.com
authors.forename: Shao-Bin
authors.initials: SB
authors.lastname: Duan
authors.forename: Gai-Ling
authors.initials: GL
authors.lastname: Liu
authors.forename: Yu-Hui
authors.initials: YH
authors.lastname: Wang
authors.forename: Jing-Jing
authors.initials: JJ
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000473:pathology*; D003928:Diabetic Nephropathies / Q000473:pathology*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D007684:Kidney Tubules / Q000166:cytology*; D008297:Male; D018384:Oxidative Stress; D011341:Probucol / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019459:Urothelium / Q000166:cytology*
chemical_list: D000975:Antioxidants; D011341:Probucol