Changes in Intestinal Epithelial Homeostasis by an IGF1R-driven Mechanism (2012)

Undergraduate: Hannah Gavin

Faculty Advisor: P. Kay Lund
Department: Chemistry

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The basic units of intestinal epithelial morphology are villi, the finger-like projections of epithelium into the lumen of the intestine, and crypts, or invaginations into the epithelium. Intestinal epithelial stem cells (IESC) lie at the base of the crypts directing growth and renewal of the intestine. The insulin and insulin-like growth factor 1 (IGF1) signaling pathways play key roles in regulating cell growth, proliferation, and death/apoptosis in tissues including the intestine and colon. We hypothesize that high-fat diet (HFD) and associated increases in insulin or free IGF1 impact stem cell-crypt- villus homeostasis through expansion of the IESC and enteroendocrine cell lineages by an IGF1R-driven mechanism. This hypothesis is tested using the novel Sox9-EGFP reporter mouse, which for the first time allows the direct visualization, quantification and isolation of the IESC population. The study employs flow cytometry and histology to quantify effects of HFD on the intestinal cell populations. Histology is utilized to determine effects on intestinal morphology. RNA extraction, reverse transcription and quantitative real-time PCR are performed to determine expression levels of key genes. In addition to providing valuable insight into the impact of HFD on intestinal stem and endocrine cells and signal transduction pathways, study results have potential to aid in the elucidation of the mechanisms by which HFD, obesity and hyperinsulinema promote colorectal cancer.