Sonic hedgehog signaling controls gut epithelium homeostasis following intestinal ischemia–reperfusion in a rat
Authors: Arnold G Coran
Yoav Ben-Shahar
Ilan N Bejar
Arie Bitterman
Igor Sukhotnik
Yulia Pollak
Journal: Pediatric Surgery International (2019)
Discipline: CLINICAL MEDICINE
Keywords: Apoptosis; Intestine; Ischemia–reperfusion; Sonic hedgehog; Stem cells.
Affiliations: Laboratory of intestinal adaptation and recovery, The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel., Department of Pediatric Surgery, Bnai Zion Medical Center, Haifa, Israel., Department of General Surgery, Carmel Medical Center, Haifa, Israel., Section of Pediatric Surgery and Internal Medicine, C.S. Mott Children's Hospital, University of Michigan Medical School, Ann Arbor, MI, USA., Laboratory of intestinal adaptation and recovery, The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel. ., Department of Pediatric Surgery, Bnai Zion Medical Center, Haifa, Israel. .

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. 

Retracted: No

PubPeer comments:
 This paper is part of a set of at least 3 papers that appear to share microscopy images. All papers list Igor Sukhotnik as an author. Boxes of the same color highlight areas in microscopy panels that look similar. Could the authors please clarify if these are all representing the same experiments, over a period of 12 years? * Sukhotnik I et al., Pediatr Surg Int (2007) 23:473u2013478, DOI: 10.1007 s00383-006-1863-9 * Sukhotnik I et al., Dig Dis Sci (2007) 52:1497u20131504, DOI: 10.1007 s10620-006-9629-8 * Benu2010Shahar Y et al., Pediatric Surgery International (2019), DOI: 10.1007 s00383-018-4406-2 ![file] ,