Growth Factors in Gut Adaptation

描述(申请人提供)：手术切除新生儿或成人的部分小肠，使剩余的肠道适应。我们认为成纤维细胞生长因子10在这一适应过程中起着关键作用，为术后增强肠道功能的新疗法开辟了道路。这项建议侧重于成纤维细胞生长因子10(FGF10)信号在小肠切除后肠道适应中的作用。我们的初步数据表明，Fgf10在小肠切除后的回肠隐窝中异位表达，这表明这种生长因子在适应过程中发挥了重要作用。 中心假说：FGF10/FGFR2b信号是成年小鼠小肠切除后肠道适应中肠上皮祖细胞存活、增殖和分化的关键调节因子。 目的：通过条件性基因敲除FGFR2b，探讨FGFR2b信号在成年小鼠小肠切除后肠道适应中的作用。 目的：利用FGF10在成年小鼠肠上皮细胞中的功能变化，探讨FGF10在成年小鼠小肠切除后肠适应中的再生作用。 公共卫生相关性：小肠切除后剩余肠道的适应性是导致此类手术所致病理生理后果的一个重要因素。我们的建议重点是FGFR2b信号通路在肠道适应过程中的作用。阐明FGF10在肠道适应过程中对上皮细胞的作用机制，将有助于确定这一途径在小肠综合征患者中的突变，以及开发创新的治疗方法，以增强小肠切除后的肠道适应。手术切除新生儿或成人的部分小肠，导致剩余肠道的适应。我们认为成纤维细胞生长因子10在这一适应过程中起着关键作用，为术后增强肠道功能的新疗法开辟了道路。这项建议侧重于成纤维细胞生长因子10(FGF10)信号在小肠切除后肠道适应中的作用。我们的初步数据表明，Fgf10在小肠切除后的回肠隐窝中异位表达，这表明这种生长因子在适应过程中发挥了重要作用。

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.