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Accelerated cell turnover 48 h after intestinal ischemia is NOTCH independent

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Abstract

Aim of the study

Notch signaling plays important roles in maintaining intestinal epithelial homeostasis. When Notch signaling is blocked, proliferation ceases and epithelial cells become secretory. The purpose of the present study was to evaluate the role of Notch signaling pathway following intestinal ischemia–reperfusion (IR) injury in a rat model.

Materials and methods

Male Sprague–Dawley rats were randomly divided into four experimental groups: Sham-24 and Sham-48 rats underwent laparotomy and were killed 24 or 48 h later, respectively; IR-24 and IR-48 rats underwent occlusion of SMA and portal vein for 30 min followed by 24 or 48 h of reperfusion, respectively. Enterocyte proliferation and enterocyte apoptosis were determined at killing. Notch-related gene and protein expression were determined using Real Time PCR, Western blotting and immunohistochemistry 48 h followed IR.

Main results

IR-48 rats demonstrated significantly increased rates of cell proliferation and increased cell apoptosis in both jejunum and ileum compared to Sham rats. IR-48 rats exhibited a significant decrease in Notch-1 protein expression (Western blot) that was coincided with a significant decrease in the number of Notch-1 positive cells (immunohistochemistry) in jejunum (35% decrease, p < 0.05) and ileum (twofold decrease, p < 0.05) as well as Hes-1 positive cells in jejunum (28% decrease, p < 0.05) and ileum (31% decrease, p < 0.05) compared to Sham-48 rats.

Conclusions

Forty-eight hours following intestinal IR in rats, accelerated cell turnover was associated by inhibited Notch signaling pathway. Intestinal stem cells differentiation toward secretory progenitors rather than differentiation toward absorptive cells is important at this phase of intestinal recovery.

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Authors and Affiliations

  1. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    Y. Pollak & I. Sukhotnik

  2. Department of Pediatric Surgery B, Dana-Dwek Children’s Hospital, Tel Aviv Sourasky Medical Center, 6 Weizmann st, 6423906, Tel Aviv, Israel

    Y. Ben-Shahar, T. Koppelman, A. E. Fuhrer & I. Sukhotnik

  3. Department of Physiology, The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel

    Y. Ben-Shahar, Z. Abassi, A. Bitterman, H. Kreizman-Shefer & L. Hayari

Authors
  1. Y. Ben-Shahar
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  2. Z. Abassi
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  3. Y. Pollak
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  4. A. Bitterman
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  5. H. Kreizman-Shefer
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  6. T. Koppelman
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  7. A. E. Fuhrer
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  8. L. Hayari
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  9. I. Sukhotnik
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Correspondence to Y. Ben-Shahar.

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Ben-Shahar, Y., Abassi, Z., Pollak, Y. et al. Accelerated cell turnover 48 h after intestinal ischemia is NOTCH independent. Pediatr Surg Int 35, 1413–1420 (2019). https://doi.org/10.1007/s00383-019-04569-z

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  • DOI: https://doi.org/10.1007/s00383-019-04569-z

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