Anti-inflammatory effects of epidermal growth factor on the immature human intestine.
The inflammatory response of the preterm infants' intestine underlines its inability to respond to hemodynamic stress, microbes, and nutrients. Recent evidence suggests that exogenous epidermal growth factor (EGF) exerts a therapeutic influence on neonatal enteropathies. However, the molecular mechanisms underlying the beneficial effects of EGF remain to be clarified. The purpose of this study was to evaluate the impact of EGF on the gene expression profiles of the developing human small and large intestine at midgestation in serum-free organ cultures using microarrays. The gene expression profiles of cultured human fetal ileal and colonic explants were investigated in the absence or presence of a physiological concentration of 50 ng/ml EGF for 48 h. Data were analyzed with the Ingenuity Pathway Analysis (IPA) software and confirmed by qPCR. We found a total of 6,474 differentially expressed genes in the two segments in response to EGF. IPA functional analysis revealed that in addition to differentially modulating distinct cellular, molecular, and physiological functions in the small and large intestine, EGF regulated the inflammatory response in both intestinal segments in a distinct manner. For instance, several intestinal-derived chemokines such as CCL2, CCL25, CXCL5, and CXCL10 were found to be differentially regulated by EGF in the immature ileum and colon. The findings showing the anti-inflammatory influence of exogenous EGF suggests a mechanistic basis for the beneficial effects of EGF on neonatal enteropathies. These results reinforce growing evidence that by midgestation, the human small intestine and colon rely on specific and distinct regulatory pathways.
Canadian Institutes of Health Research Team on the Digestive Epithelium, Department of Anatomy and Cell Biology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Quebec, Canada.
Daniel
D
Ménard
Eric
E
Tremblay
Emanuela
E
Ferretti
Corentin
C
Babakissa
Nancy
N
Perron
Ernest G
EG
Seidman
Emile
E
Levy
Jean-François
JF
Beaulieu
D018932:Chemokine CCL2 / Q000378:metabolism; D054357:Chemokine CXCL10 / Q000378:metabolism; D054365:Chemokine CXCL5 / Q000378:metabolism; D019742:Chemokines, CC / Q000378:metabolism; D003106:Colon / Q000187:drug effects / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D007082:Ileum / Q000187:drug effects / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000187:drug effects* / Q000196:embryology; D009924:Organ Culture Techniques
C108074:CCL25 protein, human; D018932:Chemokine CCL2; D054357:Chemokine CXCL10; D054365:Chemokine CXCL5; D019742:Chemokines, CC; D004815:Epidermal Growth Factor