title: Netrin-1 attenuates the progression of renal dysfunction by inhibiting peritubular capillary loss and hypoxia in 5/6 nephrectomized rats.
abstract: OBJECTIVE
  The aim of this study was to investigate the effect of netrin-1 on peritubular capillary (PTC) loss and hypoxia in 5/6 nephrectomized (Nx) rats.
  
  
  METHODS
  Male Sprague-Dawley rats were divided into three groups (n = 10 rats/group): sham-operated rats treated with control adenovirus; 5/6 Nx rats treated with control adenovirus; and 5/6 Nx rats treated with recombinant adenovirus mediated netrin-1 gene (Ad-netrin-1) therapy. Rats were killed 12 weeks after surgery. Blood urea nitrogen (BUN), serum creatinine (Scr) and 24-h urinary albumin excretion rates were measured. Pathological changes in renal tissues were analyzed histologically. The concentration of netrin-1, CD34, and hypoxia-inducible factor-1α (HIF-1α) were analyzed by immunohistochemistry, Western blotting and real-time PCR.
  
  
  RESULTS
  Renal function and histopathological damage were significantly improved in Adnetrin-1 treated 5/6 Nx rats, compared with rats treated with the control adenovirus in the 5/6 Nx group. Furthermore, Ad-netrin-1 treatment induced a significant increase in renal PTC density, accompanied by a significant decrease in HIF-1α expression.
  
  
  CONCLUSIONS
  Adenovirus mediated netrin-1 treatment attenuates PTC damage, relieves tissues hypoxia and improves renal function, thus alleviating renal pathological changes and interstitial fibrosis in 5/6 Nx rats.
authors.affiliation: Department of Nephrology, First Affiliated Hospital of China Medical University, Shenyang, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Cao
authors.forename: Jiangmin
authors.initials: J
authors.lastname: Feng
authors.forename: Jiuxu
authors.initials: J
authors.lastname: Bai
authors.forename: Li
authors.initials: L
authors.lastname: Sun
authors.forename: Shu
authors.initials: S
authors.lastname: Li
authors.forename: Jianfei
authors.initials: J
authors.lastname: Ma
authors.forename: Lining
authors.initials: L
authors.lastname: Wang
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D002196:Capillaries / Q000503:physiopathology*; D004195:Disease Models, Animal; D018450:Disease Progression; D015316:Genetic Therapy; D000860:Hypoxia / Q000503:physiopathology / Q000517:prevention & control*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007674:Kidney Diseases / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy; D007684:Kidney Tubules / Q000098:blood supply* / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D009389:Neovascularization, Pathologic / Q000503:physiopathology / Q000517:prevention & control*; D009392:Nephrectomy; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D000075388:Netrin-1; D051381:Rats; D017207:Rats, Sprague-Dawley; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*
chemical_list: D018952:Antigens, CD34; C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009414:Nerve Growth Factors; C000617354:Ntn1 protein, rat; D025521:Tumor Suppressor Proteins; D000075388:Netrin-1