title: Reducing serum uric acid attenuates TGF-β1-induced profibrogenic progression in type 2 diabetic nephropathy.
abstract: BACKGROUND
  The pivotal role of transforming growth factor-β1 (TGF-β1)-induced tubulointerstitial fibrosis in the progression of chronic kidney disease is an active topic of research. Recent evidence indicates that hyperuricemia is associated with increased TGF-β1 and progressive tubulointerstitial injury. We examined the hypothesis that lowering serum uric acid attenuates TGF-β1-induced profibrogenic tubular change in type 2 diabetic nephropathy.
  
  
  METHODS
  KK-A(y)/Ta mice, an animal model of type 2 diabetes, were provided access to either regular drinking water or drinking water containing 10 mg/dl of allopurinol. Normal rat kidney epithelial cells were cultured and stimulated with 5 mM uric acid with or without allopurinol.
  
  
  RESULTS
  Type 2 diabetic mice that received allopurinol exhibited smaller increases in urinary albumin:creatinine ratio than diabetic control mice, as well as attenuated TGF-β1 and Smad pathway-induced profibrogenic tubular changes in diabetic kidneys. Allopurinol attenuated TGF-β1-induced Smad pathway activation in tubular cells. These findings were related to increases in E-cadherin, and decreases in vimentin and α-smooth muscle actin. Uric acid-induced upregulation of TGF-β1 depends on mitogen-activated protein kinase signaling.
  
  
  CONCLUSIONS
  This is the first study to demonstrate that reducing serum uric acid has preventive effects against to profibrogenic progression in type 2 diabetic kidney disease. These findings suggest that lowering serum uric acid may be an effective therapeutic intervention to prevent the progression of type 2 diabetic kidney disease.
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Kyung Hee University Hospital at Gangdong, College of Medicine, Seoul, Korea.
authors.forename: Su-Mi
authors.initials: SM
authors.lastname: Kim
authors.forename: Young-Wook
authors.initials: YW
authors.lastname: Choi
authors.forename: Hwa-Young
authors.initials: HY
authors.lastname: Seok
authors.forename: Kyung-Hwan
authors.initials: KH
authors.lastname: Jeong
authors.forename: Sang-Ho
authors.initials: SH
authors.lastname: Lee
authors.forename: Tae-Won
authors.initials: TW
authors.lastname: Lee
authors.forename: Chun-Gyoo
authors.initials: CG
authors.lastname: Ihm
authors.forename: Sung Jig
authors.initials: SJ
authors.lastname: Lim
authors.forename: Ju-Young
authors.initials: JY
authors.lastname: Moon
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D002478:Cells, Cultured; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000473:pathology; D003928:Diabetic Nephropathies / Q000097:blood* / Q000473:pathology; D004195:Disease Models, Animal; D018450:Disease Progression; D051379:Mice; D008815:Mice, Inbred Strains; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D014527:Uric Acid / Q000097:blood*
chemical_list: D015415:Biomarkers; D053773:Transforming Growth Factor beta1; D014527:Uric Acid