Éric Tremblay1, Emanuela Ferretti2, Corentin Babakissa3, Karolina Maria Burghardt4, Emile Levy5, Jean-François Beaulieu6. 1. Laboratory of Intestinal Physiopathology, Faculté de médecine et sciences de la santé, Université de Sherbrooke, Main Building Room 9425, Sherbrooke, QC, J1H 5N4, Canada. 2. Division of Neonatology, Department of Pediatrics, CHEO, Ottawa, ON, Canada. 3. Department of Pediatrics, Faculté de médecine et sciences de la santé, Université de Sherbrooke, Sherbrooke, QC, Canada. 4. Division of Gastroenterology, Hepatology & Nutrition, CHEO, Ottawa, ON, Canada. 5. Department of Nutrition, Centre de Recherche, CHU Sainte-Justine, Université de Montréal, Montréal, QC, Canada. 6. Laboratory of Intestinal Physiopathology, Faculté de médecine et sciences de la santé, Université de Sherbrooke, Main Building Room 9425, Sherbrooke, QC, J1H 5N4, Canada. jean-francois.beaulieu@usherbrooke.ca.
Abstract
OBJECTIVE: Necrotizing enterocolitis (NEC) is the most frequent life-threatening gastrointestinal disease experienced by premature infants in neonatal intensive care units all over the world. The objective of the present study was to take advantage of RNA-Seq data from the analysis of intestinal specimens of preterm infants diagnosed with NEC. Function enrichments with Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes were used to analyse previous data in order to identify biological and functional processes, which could provide more insight into the pathogenesis of NEC in infants. RESULTS: Gene set enrichment analysis indicated that the most significant biological pathways over-represented in NEC neonates were closely associated with innate immune functions. One of the striking observations was the highly modulated expression of inflammatory genes related to the IL-17 pathway including such as pro-inflammatory cytokines (CXCL8), chemokines (CXCL5 and CXCL10) and antimicrobials (DEF5A, DEF6A, LCN2, NOS2) in the intestine of neonates diagnosed with NEC. Interestingly, the increase in IL-17 expression appeared to be under the IL-17F form, as reported in Crohn's disease, another inflammatory bowel disease. Further investigation is thus still needed to determine the precise role of IL-17F and its downstream targets in NEC.
OBJECTIVE:Necrotizing enterocolitis (NEC) is the most frequent life-threatening gastrointestinal disease experienced by premature infants in neonatal intensive care units all over the world. The objective of the present study was to take advantage of RNA-Seq data from the analysis of intestinal specimens of preterm infants diagnosed with NEC. Function enrichments with Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes were used to analyse previous data in order to identify biological and functional processes, which could provide more insight into the pathogenesis of NEC in infants. RESULTS: Gene set enrichment analysis indicated that the most significant biological pathways over-represented in NEC neonates were closely associated with innate immune functions. One of the striking observations was the highly modulated expression of inflammatory genes related to the IL-17 pathway including such as pro-inflammatory cytokines (CXCL8), chemokines (CXCL5 and CXCL10) and antimicrobials (DEF5A, DEF6A, LCN2, NOS2) in the intestine of neonates diagnosed with NEC. Interestingly, the increase in IL-17 expression appeared to be under the IL-17F form, as reported in Crohn's disease, another inflammatory bowel disease. Further investigation is thus still needed to determine the precise role of IL-17F and its downstream targets in NEC.
Entities:
Keywords:
Gene expression; Human intestine; Interleukin-17; Preterm newborn; Transcriptomics
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