TY - JOUR
T1 - Changes in hepatic cell junctions structure during experimental necrotizing enterocolitis
T2 - Effect of EGF treatment
AU - Ludmila, Khailova
AU - Katerina, Dvorak
AU - Arganbright, Kelly M.
AU - Williams, Catherine S.
AU - Halpern, Melissa D.
AU - Bohuslav, Dvorak
PY - 2009/8
Y1 - 2009/8
N2 - 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. EGFmediated reduction of experimental NEC is associated with protection of hepatic integrity and structure.
AB - 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. EGFmediated reduction of experimental NEC is associated with protection of hepatic integrity and structure.
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U2 - 10.1203/PDR.0b013e3181aa3198
DO - 10.1203/PDR.0b013e3181aa3198
M3 - Article
C2 - 19390485
AN - SCOPUS:70349904879
SN - 0031-3998
VL - 66
SP - 140
EP - 144
JO - Pediatric Research
JF - Pediatric Research
IS - 2
ER -