Accelerated Intestinal Epithelial Cell Turnover Correlates with Stimulated BMP Signaling Cascade following Intestinal Ischemia–Reperfusion in a Rat
Authors: Yoav Ben-Shahar
Igor Sukhotnik
Hila Kreizman Shefer
Zaid Abassi
Udayan Bhattacharya
Yulia Pollak
Journal: European Journal of Pediatric Surgery (2020)
Discipline: CLINICAL MEDICINE
Keywords: Bone morphogenetic proteins (BMPs); intestinal ischemia-reperfusion (IR); rat model; enterocyte proliferation; apoptosis
Affiliations: Laboratory of Intestinal Adaptation and Recovery, Technion Israel Institute of Technology Ruth and Bruce Rappaport Faculty of Medicine, Haifa, Haifa, Israel., Department of Pediatric Surgery, Dana-Dwek Children's Hospital, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel., Laboratory of Intestinal Adaptation and Recovery, Tel Aviv University Sackler Faculty of Medicine, Tel Aviv, Israel.

Abstract:  Introduction: Bone morphogenetic proteins (BMPs) are a family of proteins that regulate proliferation and differentiation of intestinal epithelial cells. The purpose of this study was to evaluate the role of BMP signaling following intestinal ischemia-reperfusion (IR) in a rat model. Materials and methods: Male Sprague-Dawley rats were divided into four experimental groups: Sham-24 and Sham-48 rats underwent laparotomy and were sacrificed 24 or 48 hours later, respectively; IR-24 and IR-48 rats underwent occlusion of superior mesenteric artery and portal vein for 30 minutes followed by 24 or 48 hours of reperfusion, respectively. Enterocyte proliferation and apoptosis were determined at sacrifice. BMP-related genes and protein expression were determined using real-time polymerase chain reaction, Western blot, and immunohistochemistry for 48 hours followed by IR. Results: IR rats demonstrated a significant increase in BMP2 (twofold increase, p &lt; 0.05), BMP4 (sevenfold increase), STAT3 (70% increase), BMPR1 (70% increase) messenger ribonucleic acid levels in jejunum and was accompanied by a significant increase in BMP2 and BMP4 protein levels in jejunum (sixfold increase) (Western blot) and upward increase in the number of BMP-positive cells (by immunohistochemistry) in jejunal (48% increase) and ileal (56% increase) villi compared with Sham-48 animals. Elevation in BMP2 and BMP4 levels was associated with increased rates of cell proliferation and increased cell apoptosis. Conclusion: Forty-eight hours following intestinal IR in rats, BMP signaling pathway was stimulated. The increase in BMP signaling pathway activity correlates with accelerated cell turnover. 

Retracted: No

PubPeer comments:
 This paper appears to be part of a set of at least 17 papers that appear to share immunohistochemistry images. All papers list Igor Sukhotnik as an author and they span a period of 14 years. The images do not always represent the same experiments. 1. Sukhotnik I et al., Pediatr Surg Int (2005) 21: 132u2013137, DOI: 10.1007 s00383-004-1308-2 2. Sukhotnik I et al., Journal of Surgical Research (2005), DOI: 10.1016 j.jss.2005.04.032 3. Sukhotnik I et al., Journal of Surgical Research (2007), DOI: 10.1016 j.jss.2007.02.002 4. Mogilner JG et al., Journal of Pediatric Surgery (2007), DOI: 10.1016 j.jpedsurg.2007.03.035 5. Sukhotnik I et al., Dig Dis Sci (2008), DOI: 10.1007 s10620-007-9990-2 6. Sukhotnik I et al., Cancer Biology Therapy (2009), DOI: 10.4161 cbt.8.10.8128 7. Sukhotnik I et al., Journal of Pediatric Surgery (2011), DOI: 10.1016 j.jpedsurg.2010.09.051 8. Ben-Lulu S et al., PLOS ONE (2012), DOI: 10.1371 journal.pone.0045221 9. Koppelman T et al., BMC Gastroenterology (2012), DOI: 10.1186 1471-230X-12-41 10. Koppelman T et al., British Journal of Nutrition (2013), DOI: 10.1017 S0007114512000542 11. Swaid F et al., Nutrition Metabolism (2013), DOI: 10.1186 1743-7075-10-53 12. Sukhotnik I et al., Nutrition Metabolism (2014), DOI: 10.1186 1743-7075-11-17 13. Sukhotnik I et al., PLOS ONE (2014), DOI: 10.1371 journal.pone.0110675 14. Sukhotnik I et al., European Journal of Pediatric Surgery (2016), DOI: 10.1055 s-0036-1587588 15. Ben Shahar Y et al., European Journal of Pediatric Surgery (2016), DOI: 10.1055 s-0035-1559886 16. Sukhotnik I et al., Food Nutrition Research (2018), DOI: 10.29219 fnr.v62.1327 17. Ben-Shahar Y et al., European Journal of Pediatric Surgery (2019), DOI: 10.1055 s-0039-1700550 Here are four collages of the IHC figures from these papers, with boxes of the same color highlighting panels that look more similar than expected. * Collage 1: ![file] * Collage 2: ![file] * Collage 3: ![file] * Collage 4: ![file] ,