FGF‐10 protects the intestinal epithelium from LPS‐induced injury (902.14)

Abstract

Necrotizing enterocolitis (NEC) is a major cause of death among premature infants and is characterized by epithelial cell death, barrier damage and inflammation. There is no proven therapeutic approach identified for NEC. Fibroblast Growth Factor 10 (FGF10) is a soluble growth factor that enhances epithelial cell proliferation and survival during colon development. We hypothesized that FGF10 enhances epithelial cell survival and decreases inflammation following insults in the small intestine. We tested this hypothesis with an in vivo model in which rtTA Tet(O)Fgf10 and rtTA mice were fed doxycycline containing diet for 16 hours to induce Fgf10, and then injected with LPS for 90 minutes to induce acute enteritis and epithelial apoptosis. To define FGF10’s role specifically in intestinal epithelial cells, we challenged IEC‐6 rat ileal crypt cells with LPS +/‐ recombinant FGF10 and measured cell death. In vivo, Fgf10 overexpression blocked LPS‐induced loss of villus integrity and decreased the number of caspase‐3 positive cells. The inflammatory mediators Tnf, Il‐6, Tlr2 and Tlr4 were elevated in the mice challenged with LPS, a response that was inhibited by Fgf10 overexpression. In vitro, FGF10 reduced LPS‐induced IEC‐6 cell death. In conclusion, FGF10 increases cell survival and decreases inflammatory mediators, which may be useful in future therapeutic interventions for NEC.