Accelerated intestinal epithelial cell turnover after bowel resection in a rat is correlated with inhibited hedgehog signaling cascade
| Autor: | Tatiana Dorfman, Arnold G. Coran, Salim Halabi, Igor Sukhotnik, H. Kreizman Shefer, Drora Berkowitz, Yulia Pollak |
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| Rok vydání: | 2016 |
| Předmět: |
Male
Short Bowel Syndrome 0301 basic medicine medicine.medical_specialty Enterocyte medicine.medical_treatment Biology Real-Time Polymerase Chain Reaction Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine Internal medicine Intestine Small Gene expression medicine Animals Hedgehog Proteins Postoperative Period Hedgehog Cell Proliferation Epithelial Cells General Medicine Bowel resection Short bowel syndrome medicine.disease Hedgehog signaling pathway Rats Disease Models Animal Enterocytes 030104 developmental biology Endocrinology medicine.anatomical_structure Pediatrics Perinatology and Child Health Cancer research 030211 gastroenterology & hepatology Surgery Signal transduction Stem cell Signal Transduction |
| Zdroj: | Pediatric Surgery International. 32:1133-1140 |
| ISSN: | 1437-9813 0179-0358 |
| Popis: | 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). 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. 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. 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. |
| Databáze: | OpenAIRE |
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