Y Ben-Shahar1,2, Z Abassi3, Y Pollak4, A Bitterman3, H Kreizman-Shefer3, T Koppelman5, A E Fuhrer5, L Hayari3, I Sukhotnik4,5. 1. Department of Pediatric Surgery B, Dana-Dwek Children's Hospital, Tel Aviv Sourasky Medical Center, 6 Weizmann st, 6423906, Tel Aviv, Israel. yoav_bs@hotmail.com. 2. Department of Physiology, The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel. yoav_bs@hotmail.com. 3. Department of Physiology, The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel. 4. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. 5. Department of Pediatric Surgery B, Dana-Dwek Children's Hospital, Tel Aviv Sourasky Medical Center, 6 Weizmann st, 6423906, Tel Aviv, Israel.
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.
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.
Authors: Marc van de Wetering; Elena Sancho; Cornelis Verweij; Wim de Lau; Irma Oving; Adam Hurlstone; Karin van der Horn; Eduard Batlle; Damien Coudreuse; Anna Pavlina Haramis; Menno Tjon-Pon-Fong; Petra Moerer; Maaike van den Born; Gwen Soete; Steven Pals; Martin Eilers; Rene Medema; Hans Clevers Journal: Cell Date: 2002-10-18 Impact factor: 41.582
Authors: Igor Sukhotnik; Vera Brod; Michael Lurie; Michal A Rahat; Sergei Shnizer; Nitza Lahat; Jorge G Mogilner; Haim Bitterman Journal: Crit Care Med Date: 2009-03 Impact factor: 7.598
Authors: François Gerbe; Johan H van Es; Leila Makrini; Bénédicte Brulin; Georg Mellitzer; Sylvie Robine; Béatrice Romagnolo; Noah F Shroyer; Jean-François Bourgaux; Christine Pignodel; Hans Clevers; Philippe Jay Journal: J Cell Biol Date: 2011-03-07 Impact factor: 10.539