Influence of the Aryl Hydrocarbon Receptor On Epithelial Exfoliation, Proliferation, and Differentiation Within the Gastrointestinal Tract
Open Access
- Author:
- Kehs, Zoe
- Area of Honors:
- Toxicology
- Degree:
- Bachelor of Science
- Document Type:
- Thesis
- Thesis Supervisors:
- Gary H Perdew, Thesis Supervisor
Gary H Perdew, Thesis Honors Advisor
Andrew David Patterson, Faculty Reader - Keywords:
- aryl hydrocarbon receptor
toxicology
ahr
intestine
duodenum
jejunum
pharmacology
intestinal turnover
goblet cell count - Abstract:
- The Aryl Hydrocarbon Receptor (AHR) is a basic helix-loop-helix family transcription factor. AHR activation is shown to decrease shedding and increase the number of goblet cells in the small intestine, specifically the duodenum. This phenotype was examined using gene expression in a variety of mouse experiments. Shedding serves as a protective mechanism within the intestine, however, excessive shedding can lead to increased risk upon toxicant exposure. To evaluate whether the profound effect of intestinal AHR activity was due to the influence on immune or epithelial cells, markers for proliferation, differentiation, and inflammation, tight junction gene expression were viewed under the lens of mRNA expression levels in Ahr +/+ (wildtype, C57BL6/J) and Ahr -/- (knockout) mice. These were examined primarily is the duodenum as the AHR is most highly expressed in this segment of the intestinal tract. The expression levels of various marker genes analyzed via qRT-PCR suggest an important role for the AHR in epithelial cells, as there was a significant expression differences in the Ahr +/+ and Ahr -/- mice for markers that correspond to the epithelial cells, including Klf4 and Krt20, two key differentiation markers. These markers are expressed in goblet cells and is consistent with a role for the AHR in regulating goblet cell number. To further examine the role of AHR in intestinal biology, mRNA levels for various amino acid transporters were measured in duodenal scrapes, or duodenal and jejunum zonal fractions. Slc1a5, Glut1, and Slc3a1 all showed significant changes upon comparison of Ahr+/+ and Ahr -/- mice. Indolo[3,2b]carbazole exposure data utilizing the zonal fractionation of the mouse duodenum confirmed the highest areas of transporter expression in the intestine was in the crypt and ICZ induced expression in all of the fractions. Overall, these data suggest that the AHR plays a role in epithelial differentiation and goblet cell number and that AHR may have an additional role in glutamine uptake in the intestine via the SLC1A5 transporter.