title: PI3K/Akt signaling pathway is involved in the pathogenesis of ulcerative colitis.
abstract: OBJECTIVE
  The purpose of this study was to investigate the role of the PI3K/Akt signaling pathway in the pathogenesis of ulcerative colitis (UC).
  
  
  METHODS
  Mucosal biopsy specimens from 54 active UC cases and adjacent normal tissues from 18 colon cancer cases were investigated. Twenty-eight Balb/c mice were randomly divided into four groups. Dextran sulphate sodium (DSS) solution (5%) was used to develop the mouse colitis model. After treatment with wortmannin (a PI3K inhibitor), disease activity index (DAI) and histological score was determined for each group of mice. Expression of phosphorylated Akt (p-Akt) in UC patients and mouse intestinal mucosa was determined by immunohistochemical staining. We also determined the effect of wortmannin on tumor necrosis factor-α (TNF-α) expression in intestinal biopsy tissues of UC patients and mice with DSS-induced colitis.
  
  
  RESULTS
  Wortmannin significantly reduced the level of p-Akt and TNF-α in the colitis tissues of UC patients and DSS-treated mice. Wortmannin significantly alleviated the inflammation of colitis as assessed by DAI and histological score in DSS-treated mice.
  
  
  CONCLUSIONS
  The PI3K/Akt signal transduction pathway is involved in the regulation and release of pro-inflammatory cytokines such as TNF-α and plays an important role in the development and progression of UC.
authors: Department of Geriatrics, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China.
authors: Xiao Li
authors: XL
authors: Huang
authors: Jin
authors: J
authors: Xu
authors: Xiao Hui
authors: XH
authors: Zhang
authors: Bo Yun
authors: BY
authors: Qiu
authors: Lan
authors: L
authors: Peng
authors: Meng
authors: M
authors: Zhang
authors: Hua Tian
authors: HT
authors: Gan
mesh_terms: D000730:Androstadienes / Q000627:therapeutic use; D000818:Animals; D003093:Colitis, Ulcerative / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D011897:Random Allocation; D015398:Signal Transduction / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D014409:Tumor Necrosis Factor-alpha; D000077191:Wortmannin