Contribution of PDCD10 to Intestinal Homeostasis
Alex Ellerstein, 3rd-Year, Biological Sciences
- Abstract
- Cerebral cavernous malfunction (CCM) is a disease of the neurovascular system, characterized by clusters of dilated vessels in the central nervous system. Three genes have been identified in familial cases of CCM: CCM1/KRIT1, CCM2/MGC4607, and CCM3/PDCD10. The role of CCM protein signaling in endothelial cell homeostasis has been established, but their role in epithelial cells has been underexplored. Prior studies have indicated that CCM could act in the gastrointestinal tract. Specific findings demonstrate that Pdcd10 deletion influences the intestine through reduction of the mucus layer, enlargement of the goblet cells, and inflammation of the intestine. Previous findings have indicated that PDCD10 is involved in intestinal homeostasis and therefore intestinal disease development, but further studies were necessary to establish its exact role. It was hypothesized that CCM3/PDCD10 plays a role in intestinal epithelial cell (IEC) homeostasis through modulating intestinal stem cell (ISC) proliferation. Furthermore, the hypothesis indicated that PDCD10-induced disruption of IEC maintenance contributes to Inflammatory Bowel Disease (IBD). The role of CCM proteins was investigated using tamoxifen-inducible mouse knockout models, mouse weight studies, gamma radiation, immunohistochemical staining, and quantitative morphological analysis of intestinal characteristics. Furthermore, PDCD10 and other CCM protein expression levels on the GEO database were compared in control individuals and individuals with IBD. It was found that PDCD10 deletion exacerbated disruption of intestinal homeostasis in 12 Gy and 8 Gy damage-induced conditions, demonstrating the role of PDCD10 in IEC homeostasis. It was further observed that β-catenin activation in intestinal stem cells rescues the irregularities in PDCD10-deleted mice, indicating that β-catenin could act downstream of PDCD10. Finally, PDCD10 was upregulated in certain IBD cases, which could act as a compensatory event and needs to be further explored. Overall, these findings indicate a role of PDCD10 in a signaling pathway for ISC maintenance, and could contribute to development of IBD.
- Presented by
- Alex Ellerstein
- Research Mentors
- Christopher Weber, Department of Pathology, University of Chicago; Le Shen, Department of Pathology
- Keywords
- Biological & Health Sciences





























































































