Accelerated intestinal epithelial cell turnover after bowel resection in a rat is correlated with inhibited hedgehog signaling cascade
Authors: H Kreizman Shefer
A G Coran
T Dorfman
Salim Halabi
I Sukhotnik
Y Pollak
D Berkowitz
Journal: Pediatric Surgery International (2016)
Discipline: CLINICAL MEDICINE
Keywords: Adaptation; Hedgehog signaling; Intestine; Short bowel syndrome; Stem cell.
Affiliations: 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. ., 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., Department of Emergency Medicine, Carmel Medical Center, Haifa, Israel., Section of Pediatric Surgery, C.S. Mott Children's Hospital, University of Michigan Medical School, Ann Arbor, MI, USA., Department of Pediatric Gastroenterology and Nutrition, Bnai Zion Medical Center, Haifa, Israel.

Abstract:  Purpose: 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. Conclusion: 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. 

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 11 years? * Sukhotnik I et al., Digestive Diseases and Sciences (2005), DOI: 10.1007 s10620-005-3067-x * Bassel Haj et al., Pediatr Surg Int (2014) 30:181u2013183, DOI: 10.1007 s00383-013-3448-8 * Sukhotnik I et al., Pediatr Surg Int (2016), DOI: 10.1007 s00383-016-3969-z https: imgur.com T4kNVnI , 
 Dear Claire Francis You did not respond to my direct E-mail. When you told that I affect children and sent it to my administrattion without provide your personal data, you made a violation of Israeli law. My lawyer asked you again to provide us your personal information ( real name, address, phone number, ID) and we can start a trial process. If you will not provide us information about yourself in next 24 hours, we will address to Internet Crime Dept of Israeli Police to find you Sincerely Sukhotnik I, MD , 
 Dear Dr. Sukhotnik, Not sure why you reply to my email with  Dear Claire Francis , and not by my name, since I am not Claire Francis. I also did not get an email from you, but I am happy to discuss these matters with you in the open. I cannot imagine that I violated Israeli law in any way, since I have never been in Israel, but please tell me what I did wrong. I am sure the Israel Internet Crime Department has other priorities than to hunt down a person who did not even write this post. In fact, they might remind you to not falsely accuse the wrong person. Happy to discuss any concerns about my identity here in the open. But even better, please focus on the concern about the images as shared in my first post. I will repost the image here now that the brief PubPeer image glitch has been resolved. Elisabeth Bik, California, USA ![file] , 
 Perhaps Dr. Sukhotnik is referring an email similar to that shown below, although in this there is no mention of children, and no defamatory language whatsoever. I do often send this anonymous email to institutional and or journal leadership, but have not heard from any lawyers. Although I too am not subject to Israeli law, it certainly cannot be against the law even in Israel to make a suggestion to university administrators that they consider reading the material already posted by others on this site regarding researchers at their institution. In addition, this email deliberately and explicitly states that it is **not** an accusation of misconduct. I also am not u2018Claire Francis.u2019 If your institution received emails from other anonymous persons, you will have to wait for them to respond to you. *** Link I wanted to bring to your attention more than XX discussion threads regarding papers authored by author name and others who appeared affiliated with your institution on PubPeer (a post publication journal discussion club). The researchers seem to have been notified by the PubPeer system but not to have yet addressed the issues raised. Importantly, these issues may not be signs of misconduct and a clarification by the authors may address the concerns. I am sending this to multiple parties that appear to be affiliated with this institution as it wasnu2019t made clear on your website to whom concerns of this type should be raised. On occasion I send notes of this type via blind copy to third parties who may potentially be interested. I have no affiliation with PubPeer, nor any of the institutions or individuals involved. I am only an anonymous commenter on the PubPeer site. These COPE guidelines may be useful https: doi.org 10.24318 cope.2019.2.21 , 
 #2 Could the first author offer any explanation for the image similarities described [here] ? Do you know the proper contact at the University who investigates those types of issues? *** ![file] ,