Hiromu Miyake1, Bo Li2, Carol Lee2, Yuhki Koike2, Yong Chen2, Shogo Seo2, Agostino Pierro3. 1. Division of General and Thoracic Surgery, The Hospital for Sick Children, Toronto, ON, Canada; Department of Pediatric Surgery, Shizuoka Children's Hospital, Shizuoka, Japan. 2. Division of General and Thoracic Surgery, The Hospital for Sick Children, Toronto, ON, Canada. 3. Division of General and Thoracic Surgery, The Hospital for Sick Children, Toronto, ON, Canada. Electronic address: agostino.pierro@sickkids.ca.
Abstract
BACKGROUND: Necrotizing enterocolitis (NEC) is a disease known to cause injury to multiple organs including the liver. Liver regeneration is essential for the recovery after NEC-induced liver injury. Our aim was to investigate hepatic proliferation and progenitor cell marker expression in experimental NEC. METHODS: Following ethical approval (#32238), NEC was induced in mice by hypoxia, gavage feeding of hyperosmolar formula, and lipopolysaccharide. Breastfed pups were used as control. We analyzed serum ALT level, liver inflammatory cytokines, liver proliferation markers, and progenitor cell marker expression. Comparison was made between NEC and controls. RESULTS: Serum ALT level was higher in NEC (p<0.05). The mRNA expression of inflammatory cytokines in the liver was also higher in NEC (IL6: p<0.05, TNF-α: p<0.01). Conversely, mRNA expression of proliferation markers in the liver was lower in NEC (Ki67; p<0.01, PCNA: p<0.01). LGR5 expression was also significantly decreased in NEC as demonstrated by mRNA (p<0.05) and protein (p<0.01) levels. CONCLUSIONS: Inflammatory injury was present in the liver during experimental NEC. Proliferation and LGR5 expression were impaired in the NEC liver. Modulation of progenitor cell expressing LGR5 may result in stimulation of liver regeneration in NEC-induced liver injury and improved clinical outcome. LEVEL OF EVIDENCE: Level IV.
BACKGROUND:Necrotizing enterocolitis (NEC) is a disease known to cause injury to multiple organs including the liver. Liver regeneration is essential for the recovery after NEC-induced liver injury. Our aim was to investigate hepatic proliferation and progenitor cell marker expression in experimental NEC. METHODS: Following ethical approval (#32238), NEC was induced in mice by hypoxia, gavage feeding of hyperosmolar formula, and lipopolysaccharide. Breastfed pups were used as control. We analyzed serum ALT level, liver inflammatory cytokines, liver proliferation markers, and progenitor cell marker expression. Comparison was made between NEC and controls. RESULTS: Serum ALT level was higher in NEC (p<0.05). The mRNA expression of inflammatory cytokines in the liver was also higher in NEC (IL6: p<0.05, TNF-α: p<0.01). Conversely, mRNA expression of proliferation markers in the liver was lower in NEC (Ki67; p<0.01, PCNA: p<0.01). LGR5 expression was also significantly decreased in NEC as demonstrated by mRNA (p<0.05) and protein (p<0.01) levels. CONCLUSIONS: Inflammatory injury was present in the liver during experimental NEC. Proliferation and LGR5 expression were impaired in the NEC liver. Modulation of progenitor cell expressing LGR5 may result in stimulation of liver regeneration in NEC-induced liver injury and improved clinical outcome. LEVEL OF EVIDENCE: Level IV.
Authors: Charles M Skinner; Isabelle R Miousse; Laura E Ewing; Vijayalakshmi Sridharan; Maohua Cao; Haixia Lin; D Keith Williams; Bharathi Avula; Saqlain Haider; Amar G Chittiboyina; Ikhlas A Khan; Mahmoud A ElSohly; Marjan Boerma; Bill J Gurley; Igor Koturbash Journal: Food Chem Toxicol Date: 2018-09-30 Impact factor: 6.023