title: Valsartan inhibited HIF-1α pathway and attenuated renal interstitial fibrosis in streptozotocin-diabetic rats.
abstract: OBJECTIVE
  To investigate the effect of angiotensin II AT1 receptor blocker valsartan on hypoxia-inducible factor (HIF)-1α-mediated gene activation and its association with renal interstitial fibrosis (RIF) in diabetic nephropathy rats.
  
  
  METHODS
  Sprague-Dawley rats were randomly divided into 3 groups: control (C group), streptozocin-induced diabetic nephropathy (D group), and valsartan-treated D rats (T group). At end of the 4th, 8th and 12th week 6 rats from each group were sacrificed and blood, urine and kidneys were collected. Blood glucose, serum creatinine (Scr) and 24-h urinary protein were measured and kidneys were processed for Masson-stain as well as immunohistochemistry and real time-PCR analyses of the expressions of HIF-1α, and its target genes tissue inhibitor of metalloproteinase (TIMP)-1 and endothelin (ET)-1 in the kidney.
  
  
  RESULTS
  (1) At the 4th, 8th and 12th week, the areas of RIF were significantly increased in D and T groups, which was accompanied by higher levels of 24-h urinary protein, Scr, HIF-1α, ET-1 and TIMP-1 compared with C group. (2) At the 8th and 12th week, the above changes were significantly attenuated in T group compared with D group.
  
  
  CONCLUSIONS
  Valsartan may reduce HIF-1α-mediated gene activation and consequently improve kidney damage in diabetic nephropathy rats.
authors.affiliation: Department of Nephrology, The First Affiliated Hospital, Nephrology Research Institute, Zhengzhou University, Zhengzhou, Henan 450052, PR China.
authors.forename: Lin
authors.initials: L
authors.lastname: Tang
authors.forename: Run
authors.initials: R
authors.lastname: Yi
authors.forename: Bing
authors.initials: B
authors.lastname: Yang
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.forename: Huijuan
authors.initials: H
authors.lastname: Chen
authors.forename: Zhangsuo
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D015153:Blotting, Western; D003404:Creatinine / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000473:pathology*; D003928:Diabetic Nephropathies / Q000188:drug therapy / Q000473:pathology*; D019332:Endothelin-1 / Q000378:metabolism; D015870:Gene Expression; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007150:Immunohistochemistry; D007668:Kidney / Q000187:drug effects / Q000473:pathology*; D008297:Male; D009395:Nephritis, Interstitial / Q000188:drug therapy / Q000473:pathology*; D011507:Proteinuria / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D013311:Streptozocin; D013777:Tetrazoles / Q000494:pharmacology*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000068756:Valsartan
chemical_list: D001786:Blood Glucose; D019332:Endothelin-1; C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D013777:Tetrazoles; D019715:Tissue Inhibitor of Metalloproteinase-1; D013311:Streptozocin; D000068756:Valsartan; D003404:Creatinine; D014633:Valine