title: Accelerated intestinal epithelial cell turnover after bowel resection in a rat is correlated with inhibited hedgehog signaling cascade.
abstract: OBJECTIVE
  The hedgehog (Hh) signaling pathway is one of the key regulators of gastrointestinal tract development. Recent studies point to the role of hedgehog signaling in regulating adult stem cells involved in maintenance and regeneration of intestinal stem cells. The purpose of this study was to evaluate the role of Hh signaling during intestinal adaptation in a rat model of short bowel syndrome (SBS).
  
  
  METHODS
  Male rats were divided into two groups: Sham rats underwent bowel transection and SBS rats underwent a 75 % bowel resection. Parameters of intestinal adaptation, enterocyte proliferation, and apoptosis were determined 2 weeks after operation. Illumina's Digital Gene Expression analysis was used to determine the Hh signaling gene expression profiling. Hh-related genes and protein expression were determined using Real-Time PCR, Western blotting, and immunohistochemistry.
  
  
  RESULTS
  Massive small bowel resection resulted in a significant increase in enterocyte proliferation and concomitant increase in cell apoptosis. From the total number of 20,000 probes, 13 genes related to Hh signaling were investigated. In jejunum, eight genes were down-regulated, three genes up-regulated, and two genes remained unchanged. In ileum, five genes were down-regulated and six genes were unchanged in SBS vs sham animals. SBS rats also demonstrated a significant three- to fourfold decrease in SMO, GIL, and PTCH mRNA, and protein levels (determined by Real-Time PCR and Western blot) compared to control animals.
  
  
  CONCLUSIONS
  Two weeks following massive bowel resection in rats, the accelerated cell turnover was accompanied by an inhibited Hh signaling pathway. Hh signaling may serve as an important mediator of reciprocal interactions between the epithelium and the underlying mesenchymal stroma during intestinal adaptation following massive bowel resection in a rat.
authors.affiliation: Laboratory of Intestinal Adaptation and Recovery, The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel. igor-dr@internet-zahav.net.|Department of Pediatric Surgery B, Bnai Zion Medical Center, 47 Golomb St., P.O.B. 4940, Haifa, 31048, Israel. igor-dr@internet-zahav.net.
authors.forename: I
authors.initials: I
authors.lastname: Sukhotnik
authors.affiliation: Laboratory of Intestinal Adaptation and Recovery, The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.|Department of Pediatric Surgery B, Bnai Zion Medical Center, 47 Golomb St., P.O.B. 4940, Haifa, 31048, Israel.
authors.forename: T
authors.initials: T
authors.lastname: Dorfman
authors.affiliation: Laboratory of Intestinal Adaptation and Recovery, The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.|Department of Emergency Medicine, Carmel Medical Center, Haifa, Israel.
authors.forename: Salim
authors.initials: S
authors.lastname: Halabi
authors.affiliation: Laboratory of Intestinal Adaptation and Recovery, The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Y
authors.initials: Y
authors.lastname: Pollak
authors.affiliation: Laboratory of Intestinal Adaptation and Recovery, The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: H
authors.initials: H
authors.lastname: Kreizman Shefer
authors.affiliation: Section of Pediatric Surgery, C.S. Mott Children's Hospital, University of Michigan Medical School, Ann Arbor, MI, USA.
authors.forename: A G
authors.initials: AG
authors.lastname: Coran
authors.affiliation: Department of Pediatric Gastroenterology and Nutrition, Bnai Zion Medical Center, Haifa, Israel.
authors.forename: D
authors.initials: D
authors.lastname: Berkowitz
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000502:physiology; D004195:Disease Models, Animal; D020895:Enterocytes / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism*; D053823:Hedgehog Proteins / Q000378:metabolism*; D007421:Intestine, Small / Q000378:metabolism* / Q000601:surgery; D008297:Male; D011184:Postoperative Period; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D012778:Short Bowel Syndrome / Q000378:metabolism* / Q000601:surgery*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D053823:Hedgehog Proteins
keywords: Adaptation; Hedgehog signaling; Intestine; Short bowel syndrome; Stem cell