Changes in Hepatic Cell Junctions Structure During Experimental Necrotizing Enterocolitis: Effect of EGF Treatment

• Published in: Pediatric research Vol. 66; no. 2; pp. 140 - 144
• Main Authors: Khailova, Ludmila, Dvorak, Katerina, Arganbright, Kelly M, Williams, Catherine S, Halpern, Melissa D, Dvorak, Bohuslav
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.08.2009; Lippincott Williams & Wilkins
• Subjects: alpha Catenin - metabolism; Animal Feed; Animals; basic-science-investigation; beta Catenin - metabolism; Biological and medical sciences; Cadherins - metabolism; Claudin-1; Claudin-3; Claudins; Diet; Disease Models, Animal; Enterocolitis, Necrotizing - drug therapy; Enterocolitis, Necrotizing - pathology; Epidermal Growth Factor - metabolism; Epidermal Growth Factor - pharmacology; Epidermal Growth Factor - therapeutic use; Gastroenterology. Liver. Pancreas. Abdomen; General aspects; Hepatocytes - cytology; Hepatocytes - drug effects; Humans; Intercellular Junctions - chemistry; Intercellular Junctions - drug effects; Intercellular Junctions - ultrastructure; Medical sciences; Medicine; Medicine & Public Health; Membrane Proteins - metabolism; Occludin; Other diseases. Semiology; Pediatric Surgery; Pediatrics; Phosphoproteins - metabolism; Rats; Rats, Sprague-Dawley; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tumor Necrosis Factor-alpha - metabolism; Zonula Occludens-1 Protein; Zonula Occludens-2 Protein; Human; Cell structure; Pediatrics; Digestive system; Liver; Cell junction; Necrotizing enterocolitis; Change; Experimental study; Epidermal growth factor; Newborn; Treatment; Digestive diseases; Intestinal disease
• ISSN: 0031-3998; 1530-0447
• DOI: 10.1203/PDR.0b013e3181aa3198

Necrotizing enterocolitis (NEC) is a devastating disease of premature babies. Previously, we have shown that EGF reduces NEC and that overproduction of hepatic TNF-α is associated with intestinal damage. Leakage of TNF-α may be a consequence of epithelial hepatic cellular junction dysfunction. The aim of this study was to investigate changes in the composition of hepatic tight junctions (TJs) and adherens junctions (AJs). Using an established rat model of NEC, animals were divided into the following groups: dam fed (DF), formula fed (NEC), or fed with formula supplemented with EGF (EGF). Serum EGF and histologic localization of major TJ and AJ proteins were evaluated. Distribution patterns of hepatic TJ and AJ proteins were significantly altered in the NEC group compared with those in DF or EGF groups. Cytoplasmic accumulation of occludin, claudin-2, and ZO-1 with reduction of claudin-3 signal was detected in the liver of NEC rats. Localization of β-catenin was associated with the hepatocyte membrane in EGF and DF groups, but diffused in the NEC group. These data show that hepatic cellular junctions are significantly altered during NEC pathogenesis. EGF-mediated reduction of experimental NEC is associated with protection of hepatic integrity and structure.