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

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Abstract

Purpose

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.

Results

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).

Conclusions

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.

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Funding

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

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Authors and Affiliations

  1. Laboratory of intestinal adaptation and recovery, The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel

    Yoav Ben-Shahar, Yulia Pollak, Ilan N. Bejar & Igor Sukhotnik

  2. Department of Pediatric Surgery, Bnai Zion Medical Center, Haifa, Israel

    Yoav Ben-Shahar & Igor Sukhotnik

  3. Department of General Surgery, Carmel Medical Center, Haifa, Israel

    Arie Bitterman

  4. Section of Pediatric Surgery and Internal Medicine, C.S. Mott Children’s Hospital, University of Michigan Medical School, Ann Arbor, MI, USA

    Arnold G. Coran

Authors
  1. Yoav Ben-Shahar
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  2. Yulia Pollak
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  3. Arie Bitterman
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  4. Arnold G. Coran
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  5. Ilan N. Bejar
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  6. Igor Sukhotnik
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Corresponding author

Correspondence to Igor Sukhotnik.

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Ben-Shahar, Y., Pollak, Y., Bitterman, A. et al. Sonic hedgehog signaling controls gut epithelium homeostasis following intestinal ischemia–reperfusion in a rat. Pediatr Surg Int 35, 255–261 (2019). https://doi.org/10.1007/s00383-018-4406-2

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  • DOI: https://doi.org/10.1007/s00383-018-4406-2

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