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Liver damage, proliferation, and progenitor cell markers in experimental necrotizing enterocolitis

      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.

      Key words

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