title: Activation of hypoxia-inducible factor attenuates renal injury in rat remnant kidney.
abstract: BACKGROUND
  Chronic hypoxia in the kidney has been suggested as a final common pathway to end-stage renal disease. Hypoxia-inducible factor (HIF) is a transcription factor that regulates cellular hypoxic responses, and it is a promising target with therapeutic potential in various kidney disease models. In this study, we investigated whether HIF activation could attenuate renal injury in the rat remnant kidney model.
  
  
  METHODS
  Two weeks after a subtotal nephrectomy, rats received a continuous infusion of dimethyloxalylglycine (DMOG) for 4 weeks to activate HIF.
  
  
  RESULTS
  The DMOG infusion halted the progression of proteinuria. A histological evaluation revealed that the glomerulosclerosis and tubulointerstitial injury were significantly decreased by DMOG treatment. DMOG increased renal HIF-1alpha protein. The expression of glucose transporter-1 (GLUT-1) and prolyl hydroxylase 3 (PHD3) and the immunostaining of vascular endothelial growth factor (VEGF) were increased by DMOG. DMOG-treated rats showed less podocyte injury manifested by decreased immunostaining of desmin and the restoration of podoplanin staining. Furthermore, plasma malondialdehyde (MDA), a marker of oxidative stress, showed a tendency to decrease, and the renal expression of catalase, an antioxidant, was significantly increased by DMOG. The DMOG treatment decreased macrophage infiltration and reduced fibrosis, as manifested by decreased type IV collagen and osteopontin expression.
  
  
  CONCLUSIONS
  Activation of HIF by DMOG halted the progression of proteinuria and attenuated structural damage by preventing podocyte injury in the remnant kidney model. This renoprotection was accompanied by a reduction of oxidative stress, inflammation and fibrosis.
authors.affiliation: Department of Internal Medicine and Kidney Research Institute, Hallym University College of Medicine, Anyang, Korea.
authors.forename: Young Rim
authors.initials: YR
authors.lastname: Song
authors.forename: Sun Jin
authors.initials: SJ
authors.lastname: You
authors.forename: Yun-Mi
authors.initials: YM
authors.lastname: Lee
authors.forename: Ho Joon
authors.initials: HJ
authors.lastname: Chin
authors.forename: Dong-Wan
authors.initials: DW
authors.lastname: Chae
authors.forename: Yun Kyu
authors.initials: YK
authors.lastname: Oh
authors.forename: Kwon Wook
authors.initials: KW
authors.lastname: Joo
authors.forename: Jin Suk
authors.initials: JS
authors.lastname: Han
authors.forename: Ki Young
authors.initials: KY
authors.lastname: Na
mesh_terms: D000600:Amino Acids, Dicarboxylic / Q000494:pharmacology; D000818:Animals; D002908:Chronic Disease; D004195:Disease Models, Animal; D018450:Disease Progression; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism* / Q000601:surgery*; D007674:Kidney Diseases / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D009392:Nephrectomy; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D000600:Amino Acids, Dicarboxylic; D051272:Glucose Transporter Type 1; D051793:Hypoxia-Inducible Factor 1; D042461:Vascular Endothelial Growth Factor A; C040947:oxalylglycine