title: Activation of PI3K/Akt/mTOR signaling pathway triggered by PTEN downregulation in the pathogenesis of Crohn's disease.
abstract: OBJECTIVE
  We aimed to investigate the role of the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway and its negative feedback factor, phosphatase and tensin homolog (PTEN), in the pathogenesis of Crohn's disease (CD).
  
  
  METHODS
  Peripheral blood was collected from patients with CD and healthy controls while colon tissue samples were collected from CD patients and those complaining of constipation but with normal endoscopic results. CD4⁺ T-cells were isolated from peripheral blood. The expression of PI3K/Akt/mTOR pathway components and PTEN was evaluated in the peripheral CD4⁺ T-cells using polymerase chain reaction and Western blot, and in intestinal mucosal lymphocytes using immunohistochemistry.
  
  
  RESULTS
  mRNA expressions of PI3K, Akt, mTOR, 4E-binding protein 1 (4E-BP1) and phosphate-ribosomal protein S6 kinase (p70S6K) in peripheral CD4⁺ T-cells were upregulated in CD patients compared with healthy controls . However, the differences were not significant (P > 0.05). Western blot showed that the ratios of phospho-Akt: Akt, phosphorylated-4E-BP1: 4E-BP1 and phospho-p70S6K: p70S6K in peripheral CD4⁺ T-cells were higher in CD patients (P < 0.05). The composite staining score of phospho-Akt and phospho-mTOR in intestinal mucosal lymphocytes also increased in patients with CD compared with those with constipation. Both PTEN mRNA and protein expressions in either peripheral CD4⁺ T-cells or mucosal lymphocytes were lower in patients with CD than in the healthy controls and those with constipation.
  
  
  CONCLUSIONS
  The PI3K/Akt/mTOR signaling pathway was activated in CD. The activation of the PI3K/Akt/mTOR pathway caused by PTEN downregulation may be involved in the pathogenesis of CD.
authors: Department of Gastroenterology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, China.
authors: Shun Hua
authors: SH
authors: Long
authors: Yao
authors: Y
authors: He
authors: Min Hu
authors: MH
authors: Chen
authors: Kang
authors: K
authors: Cao
authors: Yu Jun
authors: YJ
authors: Chen
authors: Bai Li
authors: BL
authors: Chen
authors: Ren
authors: R
authors: Mao
authors: Sheng Hong
authors: SH
authors: Zhang
authors: Zhen Hua
authors: ZH
authors: Zhu
authors: Zhi Rong
authors: ZR
authors: Zeng
authors: Pin Jin
authors: PJ
authors: Hu
mesh_terms: D000293:Adolescent; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D016022:Case-Control Studies; D003424:Crohn Disease / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015536:Down-Regulation / Q000502:physiology*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D018928:Immunity, Mucosal; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D012333:RNA, Messenger; D058570:TOR Serine-Threonine Kinases; C546842:MTOR protein, human; C494929:PTEN protein, human
keywords: Crohn's disease; PI3K/Akt/mTOR signaling pathway; etiology; human PTEN protein