Abstract
Background and AimsAlthough Hnf1α is crucial for pancreas and liver functions, it is believed to play a limited functional role for intestinal epithelial functions. The aim of this study was to assess the consequences of abrogating Hnf1α on the maintenance of adult small intestinal epithelial functions.Methodology/Principal FindingsAn Hnf1α knockout mouse model was used. Assessment of histological abnormalities, crypt epithelial cell proliferation, epithelial barrier, glucose transport and signalling pathways were measured in these animals. Changes in global gene expression were also analyzed. Mice lacking Hnf1α displayed increased crypt proliferation and intestinalomegaly as well as a disturbance of intestinal epithelial cell lineages production during adult life. This phenotype was associated with a decrease of the mucosal barrier function and lumen-to-blood glucose delivery. The mammalian target of rapamycin (mTOR) signalling pathway was found to be overly activated in the small intestine of adult Hnf1α mutant mice. The intestinal epithelium of Hnf1α null mice displayed a reduction of the enteroendocrine cell population. An impact was also observed on proper Paneth cell differentiation with abnormalities in the granule exocytosis pathway.Conclusions/SignificanceTogether, these results unravel a functional role for Hnf1α in regulating adult intestinal growth and sustaining the functions of intestinal epithelial cell lineages.
Highlights
The small intestinal epithelium consists of villi and crypts lined with proliferative stem and progenitor cells
Hnf1a deletion alters the architecture of adult small intestinal epithelium and leads to intestinalomegaly
Our analysis demonstrates a fundamental role for Hnf1a in regulating adult intestinal epithelium functions including enterocyte barrier and metabolic functions, enteroendocrine cell specification and Paneth cell maturation
Summary
The small intestinal epithelium consists of villi and crypts lined with proliferative stem and progenitor cells. These cells ensure constant renewal of the epithelium throughout the life of the individual [1,2]. Enterocytes express several intestinal epithelium gene products involved in carbohydrates and lipids absorption, transport and metabolism as well as in barrier integrity to ensure protection from the luminal side and optimal blood nutrient and hormone delivery to the organism. The aim of this study was to assess the consequences of abrogating Hnf1a on the maintenance of adult small intestinal epithelial functions
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
