Growth Factors in Gut Adaptation

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DESCRIPTION (provided by applicant): Surgical removal of part of the small intestine in newborn or adult leads to the adaptation of the remaining intestine. We propose that Fibroblast growth factor 10 plays a critical role in this adaptation process opening the way to new therapies to enhance gut function after resection. This proposal focuses on the role of the Fibroblast Growth Factor 10 (FGF10) signaling in gut adaptation after small bowel resection. Our preliminary data indicate that Fgf10 is ectopically expressed in the crypts of ileum after small bowel resection, suggesting a significant role for this growth factor in the adaptation process. Central Hypothesis: FGF10/FGFR2b signaling is a key regulator of intestinal epithelial progenitor cell survival, proliferation and differentiation in gut adaptation following small bowel resection in adult mice. Aim 1: To determine the functional role of FGFR2b signaling during gut adaptation following small bowel resection in adult mice using conditional knockdown of FGFR2b. Aim 2: To determine the regenerative role of FGF10 during gut adaptation following small bowel resection in adult mice by using a gain of function of Fgf10 in the adult intestinal epithelium. PUBLIC HEALTH RELEVANCE: The adaptability of the remaining intestine following small bowel resection is an important factor in the pathophysiological consequences resulting from such surgical procedure. Our proposal focuses on the role of the FGFR2b signaling pathway in the gut adaptation process. The elucidation of the mechanisms of action of FGF10 on the epithelium during the gut adaptation process will allow identifying mutations in this pathway in patients with small bowel syndrome as well as the development of innovative therapies to enhance gut adaptation after small bowel resection.Surgical removal of part of the small intestine in newborn or adult leads to the adaptation of the remaining intestine. We propose that Fibroblast growth factor 10 plays a critical role in this adaptation process opening the way to new therapies to enhance gut function after resection. This proposal focuses on the role of the Fibroblast Growth Factor 10 (FGF10) signaling in gut adaptation after small bowel resection. Our preliminary data indicate that Fgf10 is ectopically expressed in the crypts of ileum after small bowel resection, suggesting a significant role for this growth factor in the adaptation process.