Pediatric Surgery International

, Volume 35, Issue 2, pp 255–261 | Cite as

Sonic hedgehog signaling controls gut epithelium homeostasis following intestinal ischemia–reperfusion in a rat

  • Yoav Ben-Shahar
  • Yulia Pollak
  • Arie Bitterman
  • Arnold G. Coran
  • Ilan N. Bejar
  • Igor SukhotnikEmail author
Original Article



One of the major regulators of gastrointestinal tract development is the hedgehog signaling pathway. The purpose of this study was to evaluate the role of sonic hedgehog (SHh) signaling 24 and 48 h following intestinal ischemia–reperfusion (IR) in a rat.

Materials and methods

Male rats were divided into four experimental groups: (1) Sham-24 h rats underwent laparotomy and were sacrificed after 24 h, (2) Sham-48h rats underwent laparotomy and were sacrificed after 48 h, (3) IR-24h rats underwent occlusion of both superior mesenteric artery and portal vein for 20 min followed by 24 h of reperfusion, and (4) IR-48 h rats underwent ischemia for 20 min followed by 48 h of reperfusion. Intestinal structural changes, enterocyte proliferation and enterocyte apoptosis were determined by immunohistochemistry 24 and 48 h following IR. SHh-related genes and protein expression were determined using real-time PCR, Western blot and immunohistochemistry.


IR-24 rats demonstrated a significant decrease in Shh, Ihh, GIL and Ptch2 mRNA in jejunum and ileum compared to Sham-24 animals that was accompanied by a significant decrease in the number of SHH-positive cells (Immunohistochemistry) in jejunum (2.5-fold decrease) and ileum (37%). After 48 h, IR rats demonstrated a significant increase in Dhh, Ihh, Gil and PTCH2 mRNA in jejunum as well as in Dhh, Ihh, SMO, GIL, PTCH2 mRNA in ileum compared to IR-24 animals that was coincided with increased number of SHH-positive cells in jejunum (2.6-fold increase) and ileum (1.4-fold increase).


24 h following intestinal IR, inhibited cell turnover was associated with inhibited SHh signaling pathway. Signs of intestinal recovery appeared 48 h after IR and were correlated with increase in SHh signaling pathway activity.


Ischemia–reperfusion Intestine Sonic hedgehog Stem cells Apoptosis 



This research did not receive any specific grant from funding agencies in the public, commercial, or not- for-profit sectors.

Compliance with ethical standards

Conflict of interest

The author(s) declare that they have no conflict of interest.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Yoav Ben-Shahar
    • 1
    • 2
  • Yulia Pollak
    • 1
  • Arie Bitterman
    • 3
  • Arnold G. Coran
    • 4
  • Ilan N. Bejar
    • 1
  • Igor Sukhotnik
    • 1
    • 2
    Email author
  1. 1.Laboratory of intestinal adaptation and recovery, The Bruce Rappaport Faculty of MedicineTechnion-Israel Institute of TechnologyHaifaIsrael
  2. 2.Department of Pediatric Surgery, Bnai Zion Medical CenterHaifaIsrael
  3. 3.Department of General SurgeryCarmel Medical CenterHaifaIsrael
  4. 4.Section of Pediatric Surgery and Internal Medicine, C.S. Mott Children’s HospitalUniversity of Michigan Medical SchoolAnn ArborUSA

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