title: Ischemic preconditioning increased the intestinal stem cell activities in the intestinal crypts in mice.
abstract: BACKGROUND
  Ischemic preconditioning (IPC) can protect against ischemia-reperfusion injury in the small intestine. Because intestinal stem cells (ISCs) control the recovery and growth of intestinal villi, this study investigated whether IPC had any effects on the activity of ISCs.
  
  
  METHODS
  The small intestines of mice were treated with IPC, laparotomy only (sham), or no surgery. The crypt fractions were isolated and the characteristics of ISCs among various groups were compared. The regenerative ability and the number of organoids grown from various crypt fractions were compared. The expression of hypoxia-inducible factor-1α (HIF-1α) and the related proteins of the Wnt-/β-catenin pathway in the crypt fractions were studied.
  
  
  RESULTS
  The IPC group had higher messenger RNA levels of various stem cell markers than the sham group at days 1 and 2 after surgery. The IPC group exhibited greater regenerative activity and more crypt organoids than the sham group (P < 0.05). The expression of HIF-1α, β-catenin, and phosphoglycogen synthase kinase 3β was increased in the IPC-treated crypt fractions in vivo and cultured crypt organoid cells with deferoxamine-mimicked hypoxia in vitro.
  
  
  CONCLUSIONS
  IPC significantly upregulated the activity of ISCs, possibly through the HIF-1α response and Wnt-/β-catenin signaling pathway.
authors.affiliation: Department of Surgery, Far Eastern Memorial Hospital, Pan-Chiao, New Taipei, Taiwan, Republic of China; Department of Chemical Engineering and Materials Science, Yuan Ze University, Chung-Li, Taoyuan, Taiwan, Republic of China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Surgery, Far Eastern Memorial Hospital, Pan-Chiao, New Taipei, Taiwan, Republic of China.
authors.forename: Shih-Hua
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Department of Surgery, Far Eastern Memorial Hospital, Pan-Chiao, New Taipei, Taiwan, Republic of China; Department of Chemical Engineering and Materials Science, Yuan Ze University, Chung-Li, Taoyuan, Taiwan, Republic of China. Electronic address: yahuitsi@gmail.com.
authors.forename: Ya-Hui
authors.initials: YH
authors.lastname: Tsai
authors.affiliation: Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan, Republic of China. Electronic address: shenghongtseng@gmail.com.
authors.forename: Sheng-Hong
authors.initials: SH
authors.lastname: Tseng
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D007421:Intestine, Small / Q000098:blood supply / Q000473:pathology* / Q000601:surgery; D019194:Ischemic Preconditioning / Q000379:methods*; D007813:Laparotomy; D051379:Mice; D008810:Mice, Inbred C57BL; D008871:Microvilli / Q000473:pathology*; D009924:Organ Culture Techniques; D012333:RNA, Messenger / Q000378:metabolism; D015427:Reperfusion Injury / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D013234:Stem Cells / Q000166:cytology*; D015854:Up-Regulation / Q000502:physiology; D060449:Wnt Signaling Pathway / Q000502:physiology; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: D015415:Biomarkers; C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger; D051176:beta Catenin; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3
keywords: Intestinal stem cells; Ischemic preconditioning; Small intestine; Stem cell markers