title: The Jagged-1/Notch-1/Hes-1 pathway is involved in intestinal adaptation in a massive small bowel resection rat model.
abstract: BACKGROUND
  Notch signaling is required for the maintenance of intestinal epithelial proliferation. Dysfunction of this signaling pathway is associated with the loss of proliferated crypt epithelial cells.
  
  
  OBJECTIVE
  The aim of this study was to investigate the role of Notch signaling in small bowel resection (SBR)-associated crypt epithelial cell proliferation.
  
  
  METHODS
  Male Sprague-Dawley rats were subjected to sham operation (bowel transection and reanastomosis) or 70% mid-SBR. Intestinal tissue samples were collected at 0.5, 1, 6, 12, 24, 72, and 168 h after operation. The expression of Notch pathway mRNAs and proteins was analyzed using RT-PCR and Western blot. The expression of the Notch pathway proteins Jagged-1, NICD and Hes-1 was also determined through immunohistochemical staining using day 3 postoperative intestinal tissues. The degree of crypt epithelial cell proliferation was evaluated using the immunohistochemical staining of proliferating cell nuclear antigen (PCNA). Furthermore, IEC-6 cells were used to examine the function of the Jagged-1 signaling system.
  
  
  RESULTS
  SBR led to increased crypt epithelial cell proliferation and increased expression of Jagged-1 and Hes-1 mRNA and protein along with cleaved Notch-1. Immunohistochemical staining showed that Jagged-1, cleaved Notch-1 and Hes-1 colocalized in the same proliferated crypt epithelial cell population. Recombinant Jagged-1 significantly stimulated the proliferation of IEC-6 cells. Transient upregulation of Jagged-2 expression was found 1 h after SBR, and it was accompanied by cleaved Notch-1 and Hes-1 upregulation.
  
  
  CONCLUSIONS
  The Jagged-1/Notch-1/Hes-1 signaling pathway is involved in intestinal adaptation through increasing crypt epithelial cell proliferation.
authors.affiliation: Department of General Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China. maomaoyu1209@163.com
authors.forename: Guoqing
authors.initials: G
authors.lastname: Chen
authors.forename: Lihua
authors.initials: L
authors.lastname: Sun
authors.forename: Min
authors.initials: M
authors.lastname: Yu
authors.forename: Dan
authors.initials: D
authors.lastname: Meng
authors.forename: Wensheng
authors.initials: W
authors.lastname: Wang
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.forename: Hua
authors.initials: H
authors.lastname: Yang
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002460:Cell Line; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000502:physiology; D018398:Homeodomain Proteins / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D000072100:Jagged-1 Protein; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D051881:Receptor, Notch1 / Q000378:metabolism*; D000072099:Serrate-Jagged Proteins; D012778:Short Bowel Syndrome; D015398:Signal Transduction; D000072056:Transcription Factor HES-1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D002135:Calcium-Binding Proteins; D018398:Homeodomain Proteins; D036341:Intercellular Signaling Peptides and Proteins; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; D012333:RNA, Messenger; D051881:Receptor, Notch1; D000072099:Serrate-Jagged Proteins; D000072056:Transcription Factor HES-1; C489735:Hes1 protein, rat; C000606275:Jag1 protein, rat; C497763:Notch1 protein, rat