title: [LY294002 blocks the effect of dexamethasone in reducing urine protein in rats by inhibiting PI3K/Akt signaling pathway].
abstract: OBJECTIVE
  To investigate the involvement of PI3K/Akt signaling pathway in the changes of urine protein in adriamycin-induced nephropathic rats treated with dexamethasone and LY294002 (a PI3K inhibitor).
  
  
  METHODS
  SD rats were randomized into normal control group, ariamycin-induced nephropathy group (ADR group), ariamycin+dexamethasone group (DEX group), and ADR+DEX+LY294002 group (LY294002 group). On days 7, 14 and 28 after the treatments, 24-h urine was collected from the rats to analyze the total urine proteins. The renal tissues were obtained on day 28 to examine the expressions of p-AKT, AKT and Bad proteins in the cortical tissues using Western blotting; the expression of Bad mRNA in the cortical tissues was measured by QPCR.
  
  
  RESULTS
  Urine protein increased progressively in ADR group accompanied by significantly reduced p-AKT/AKT ratio and increased Bad mRNA expression in comparison with those in the normal control group (P<0.05). Urine protein was obviously reduced in DEX group with comparable p-AKT/AKT ratio and Bad mRNA expression level with those in the control group (P>0.05). Urine protein showed no significant reduction in LY294002 group, but the p-AKT/AKT ratio was significantly reduced and Bad mRNA expression was increased compared with those in DEX group (P<0.05).
  
  
  CONCLUSIONS
  Dexamethasone increases the expression of Bad mRNA and reduces urine protein in adriamycin-induced nephropathic rats by activating PI3K/Akt signaling pathway. LY294002 can inhibit PI3K/Akt signaling pathway to block the effect of dexamethasone, suggesting that PI3K/Akt signaling pathway is one of the signaling pathways that mediate the effect of dexamethasone on proteinuria.
authors.affiliation: Department of Pediatrics, Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, China. E-mail: liangbing1507@163.com.
authors.forename: Zhi-Gang
authors.initials: ZG
authors.lastname: Zhou
authors.forename: Wang-Li
authors.initials: WL
authors.lastname: Wu
authors.forename: Tian-Tian
authors.initials: TT
authors.lastname: Liu
authors.forename: Yun
authors.initials: Y
authors.lastname: Peng
authors.forename: Wen-Qin
authors.initials: WQ
authors.lastname: Lao
authors.forename: Min
authors.initials: M
authors.lastname: Liang
authors.forename: Mei-Hua
authors.initials: MH
authors.lastname: Zhu
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002867:Chromones / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology*; D009025:Morpholines / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D011507:Proteinuria; D051057:Proto-Oncogene Proteins c-akt; D012333:RNA, Messenger; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D051025:bcl-Associated Death Protein
chemical_list: D000893:Anti-Inflammatory Agents; D002867:Chromones; D009025:Morpholines; D012333:RNA, Messenger; D051025:bcl-Associated Death Protein; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D003907:Dexamethasone; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt