title: Protective effects of calcitriol on diabetic nephropathy are mediated by down regulation of TGF-β1 and CIP4 in diabetic nephropathy rat.
abstract: OBJECTIVE
  To explore the protective effects of calcitriol on diabetic nephropathy by modulating the expressions of transforming growth factor-beta 1 (TGF-β1) and Cdc42 interacting protein-4 (CIP4).
  
  
  METHODS
  Streptozotocin-induced diabetic nephropathy rats (n=36) were randomly divided into control group (control-H, control-M, control-L) and calcitriol group (calcitriol-H, calcitriol-M, calcitriol-L). The expression of TGF-β1 gradually decreased in control-H, control-M and control-L subgroups by injection of different virus vectors. Peanut oil and calcitriol were given to control and calcitriol group, respectively. The expressions of TGF-β1 and CIP4 in kidney, the pathology, and the renal function and lipid profiles were compared between control and calcitriol treatment groups.
  
  
  RESULTS
  In the control group, the higher level of TGF-β1 was associated with more severe glomerular pathology (P<0.05). There is a positive correlation between the expression of CIP4 and TGF-β1. Control-H subgroup had significant more severe kidney disease, higher levels of cholesterol, triglyceride, blood glucose, blood urea nitrogen (BUN) and creatinine (Cr) than control-M and control-L subgroups. After calcitriol treatment, the expression of TGF-β1 and CIP4 were significantly decreased compared to the corresponding control subgroups (all P<0.05). Renal fibrosis and pathological changes were markedly improved. The levels of cholesterol, triglyceride, blood glucose, BUN and Cr were significantly reduced (P<0.05).
  
  
  CONCLUSIONS
  Calcitriol may protect diabetic nephropathy from fibrosis via inhibition of TGF-β1 and CIP4.
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital of Xinjiang Medical University Urumqi 830054, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Yu
authors.affiliation: Department of Endocrinology, Peking Union Medical College Hospital Beijing 100730, China.
authors.forename: Jiangfeng
authors.initials: J
authors.lastname: Mao
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital of Xinjiang Medical University Urumqi 830054, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital of Xinjiang Medical University Urumqi 830054, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital of Xinjiang Medical University Urumqi 830054, China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital of Xinjiang Medical University Urumqi 830054, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhu
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001806:Blood Urea Nitrogen; D002117:Calcitriol / Q000627:therapeutic use*; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003928:Diabetic Nephropathies / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015536:Down-Regulation; D005355:Fibrosis; D006801:Humans; D007668:Kidney / Q000473:pathology; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D015778:Minor Histocompatibility Antigens / Q000378:metabolism*; D020011:Protective Agents / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D008869:Microtubule-Associated Proteins; D015778:Minor Histocompatibility Antigens; D020011:Protective Agents; D053773:Transforming Growth Factor beta1; C498640:Trip10 protein, rat; D002117:Calcitriol
keywords: Cdc42 interacting protein-4 (CIP4); Diabetic nephropathy; calcitriol; transforming growth factor beta 1 (TGF-β1)