TY - JOUR
T1 - Epidermal growth factor reduces autophagy in intestinal epithelium and in the rat model of necrotizing enterocolitis
AU - Maynard, Andrew A.
AU - Dvorak, Katerina
AU - Khailova, Ludmila
AU - Dobrenen, Holly
AU - Arganbright, Kelly M.
AU - Halpern, Melissa D.
AU - Kurundkar, Ashish R.
AU - Maheshwari, Akhil
AU - Dvorak, Bohuslav
PY - 2010/9
Y1 - 2010/9
N2 - Necrotizing enterocolitis (NEC) is a devastating intestinal disease of premature infants. Epidermal growth factor (EGF) is one of the most promising candidates in NEC prophylaxis. Autophagy regulates cell homeostasis, but uncontrolled activation of autophagy may lead to cellular injury. The aim was to evaluate the effects of EGF on intestinal autophagy in epithelial cells and in the rat NEC model and measure autophagy in NEC patients. Intestinal epithelial cells (IEC-6) and the rat NEC model were used to study the effect of EGF on intestinal autophagy. Protein levels of Beclin 1 and LC3II were measured in the intestinal epithelium in both in vivo and in vitro models. Ultrastructural changes in intestinal epithelium were studied by electron microscopy. Expression of Beclin 1, LC3II, and p62 protein was evaluated in biopsies from NEC patients. Autophagy was induced in IEC-6 cells and inhibited by adding EGF into the culture. In the rat NEC model, EGF treatment of NEC reduced expression of Beclin 1 and LC3II in ileal epithelium. Morphologically, typical signs of autophagy were observed in the epithelium of the NEC group, but not in the EGF group. A strong signal for Beclin 1 and LC3II was detected in the intestine from patients with NEC. Autophagy is activated in the intestinal epithelium of NEC patients and in the ileum of NEC rats. Supplementation of EGF blocks intestinal autophagy in both in vivo and in vitro conditions. Results from this study indicate that EGFmediated protection against NEC injury is associated with regulation of intestinal autophagy.
AB - Necrotizing enterocolitis (NEC) is a devastating intestinal disease of premature infants. Epidermal growth factor (EGF) is one of the most promising candidates in NEC prophylaxis. Autophagy regulates cell homeostasis, but uncontrolled activation of autophagy may lead to cellular injury. The aim was to evaluate the effects of EGF on intestinal autophagy in epithelial cells and in the rat NEC model and measure autophagy in NEC patients. Intestinal epithelial cells (IEC-6) and the rat NEC model were used to study the effect of EGF on intestinal autophagy. Protein levels of Beclin 1 and LC3II were measured in the intestinal epithelium in both in vivo and in vitro models. Ultrastructural changes in intestinal epithelium were studied by electron microscopy. Expression of Beclin 1, LC3II, and p62 protein was evaluated in biopsies from NEC patients. Autophagy was induced in IEC-6 cells and inhibited by adding EGF into the culture. In the rat NEC model, EGF treatment of NEC reduced expression of Beclin 1 and LC3II in ileal epithelium. Morphologically, typical signs of autophagy were observed in the epithelium of the NEC group, but not in the EGF group. A strong signal for Beclin 1 and LC3II was detected in the intestine from patients with NEC. Autophagy is activated in the intestinal epithelium of NEC patients and in the ileum of NEC rats. Supplementation of EGF blocks intestinal autophagy in both in vivo and in vitro conditions. Results from this study indicate that EGFmediated protection against NEC injury is associated with regulation of intestinal autophagy.
KW - Enteral nutrition
KW - Epithelial homeostasis
KW - Premature
KW - Small intestine
UR - http://www.scopus.com/inward/record.url?scp=77956998767&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77956998767&partnerID=8YFLogxK
U2 - 10.1152/ajpgi.00076.2010
DO - 10.1152/ajpgi.00076.2010
M3 - Article
C2 - 20539009
AN - SCOPUS:77956998767
SN - 0193-1857
VL - 299
SP - G614-G622
JO - American Journal of Physiology - Gastrointestinal and Liver Physiology
JF - American Journal of Physiology - Gastrointestinal and Liver Physiology
IS - 3
ER -