Chun-Liang Chen1, Jixin Yang2, Iyore O A James2, Hong-Yi Zhang2, Gail E Besner3. 1. Department of Pediatric Surgery, Research Institute at Nationwide Children's Hospital, Center for Perinatal Research, Nationwide Children's Hospital, The Ohio State University College of Medicine, Columbus, OH; Department of Molecular Medicine, Institute of Biotechnology, University of Texas Health Science Center at San Antonio, San Antonio, TX. 2. Department of Pediatric Surgery, Research Institute at Nationwide Children's Hospital, Center for Perinatal Research, Nationwide Children's Hospital, The Ohio State University College of Medicine, Columbus, OH. 3. Department of Pediatric Surgery, Research Institute at Nationwide Children's Hospital, Center for Perinatal Research, Nationwide Children's Hospital, The Ohio State University College of Medicine, Columbus, OH. Electronic address: gail.besner@nationwidechildrens.org.
Abstract
BACKGROUND: We have previously demonstrated that heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF) protects the intestines from injury in several different experimental animal models. In the current study, we investigated whether the ability of HB-EGF to protect the intestines from ischemia/reperfusion (I/R) injury was related to its effects on Wnt/β-catenin signaling in intestinal stem cells (ISC). METHODS: Lucien-rich repeat-containing G-protein-coupled receptor 5 (LGR5)-enhanced green fluorescent protein (EGFP) transgenic (TG) mice with fluorescently labeled ISC, as well as the same mice treated with intraluminal HB-EGF or genetically engineered to overexpress HB-EGF, were exposed to segmental mesenteric artery occlusion (sMAO) to the terminal ilium. Wnt/β-catenin signaling was evaluated using immunofluorescent staining and Western blotting. RESULTS: LGR5 expression and Wnt/β-catenin signaling in the ISC of the terminal ilium of LGR5-EGFP TG mice was significantly reduced 24 hours after sMAO. Intraluminal administration of HB-EGF or HB-EGF overexpression in these mice led to preservation of LGR5 expression and Wnt/β-catenin signaling. CONCLUSION: These data show that HB-EGF preserves Wnt/β-catenin signaling in ISC after I/R injury.
BACKGROUND: We have previously demonstrated that heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF) protects the intestines from injury in several different experimental animal models. In the current study, we investigated whether the ability of HB-EGF to protect the intestines from ischemia/reperfusion (I/R) injury was related to its effects on Wnt/β-catenin signaling in intestinal stem cells (ISC). METHODS:Lucien-rich repeat-containing G-protein-coupled receptor 5 (LGR5)-enhanced green fluorescent protein (EGFP) transgenic (TG) mice with fluorescently labeled ISC, as well as the same mice treated with intraluminal HB-EGF or genetically engineered to overexpress HB-EGF, were exposed to segmental mesenteric artery occlusion (sMAO) to the terminal ilium. Wnt/β-catenin signaling was evaluated using immunofluorescent staining and Western blotting. RESULTS:LGR5 expression and Wnt/β-catenin signaling in the ISC of the terminal ilium of LGR5-EGFP TG mice was significantly reduced 24 hours after sMAO. Intraluminal administration of HB-EGF or HB-EGF overexpression in these mice led to preservation of LGR5 expression and Wnt/β-catenin signaling. CONCLUSION: These data show that HB-EGF preserves Wnt/β-catenin signaling in ISC after I/R injury.
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