title: Changes in hepatic cell junctions structure during experimental necrotizing enterocolitis: effect of EGF treatment.
abstract: Necrotizing enterocolitis (NEC) is a devastating disease of premature babies. Previously, we have shown that EGF reduces NEC and that overproduction of hepatic TNF-alpha is associated with intestinal damage. Leakage of TNF-alpha 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 beta-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.
authors.affiliation: Department of Pediatrics, University of Arizona, Tucson, Arizona 85724, USA.
authors.forename: Ludmila
authors.initials: L
authors.lastname: Khailova
authors.forename: Katerina
authors.initials: K
authors.lastname: Dvorak
authors.forename: Kelly M
authors.initials: KM
authors.lastname: Arganbright
authors.forename: Catherine S
authors.initials: CS
authors.lastname: Williams
authors.forename: Melissa D
authors.initials: MD
authors.lastname: Halpern
authors.forename: Bohuslav
authors.initials: B
authors.lastname: Dvorak
mesh_terms: D000821:Animal Feed; D000818:Animals; D015820:Cadherins / Q000378:metabolism; D062445:Claudin-1; D062465:Claudin-3; D057167:Claudins; D004032:Diet; D004195:Disease Models, Animal; D020345:Enterocolitis, Necrotizing / Q000188:drug therapy / Q000473:pathology; D004815:Epidermal Growth Factor / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects; D006801:Humans; D007365:Intercellular Junctions / Q000737:chemistry / Q000187:drug effects / Q000648:ultrastructure; D008565:Membrane Proteins / Q000378:metabolism; D062793:Occludin; D010750:Phosphoproteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D062826:Zonula Occludens-1 Protein; D062827:Zonula Occludens-2 Protein; D051178:alpha Catenin / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
chemical_list: C568108:CLDN1 protein, human; C568122:CLDN3 protein, human; D015820:Cadherins; D062445:Claudin-1; D062465:Claudin-3; D057167:Claudins; C568114:Cldn1 protein, rat; C491874:Cldn2 protein, rat; C568124:Cldn3 protein, rat; D008565:Membrane Proteins; C568985:OCLN protein, human; D062793:Occludin; C568987:Ocln protein, rat; D010750:Phosphoproteins; C569042:TJP1 protein, human; C569046:TJP2 protein, human; C569044:Tjp1 protein, rat; D014409:Tumor Necrosis Factor-alpha; D062826:Zonula Occludens-1 Protein; D062827:Zonula Occludens-2 Protein; D051178:alpha Catenin; D051176:beta Catenin; D004815:Epidermal Growth Factor