IMP1 loss in intestinal epithelial cells promotes altered Paneth cell morphology and autophagy defects (899.2)

Abstract

Background Insulin‐like growth factor‐2 mRNA‐binding protein 1 (IMP1) is an oncofetal protein that exhibits high expression during embryonic development and lower expression in adult tissues. Mice with global Imp1‐/‐ gene deletion exhibit perinatal lethality due to altered gut morphology, suggesting a potential role in stem cell maintenance. We hypothesize that IMP1 contributes to intestinal homeostasis through modulation of the stem cell niche, specifically through a novel role in Paneth cells.Methods Using immunohistochemistry (IHC), immunofluorescense (IF), and immunoblotting, we evaluated mice with intestinal epithelial‐specific loss of Imp1 (VillinCre;Imp1floxed mice) for Paneth cell morphology (lysozyme), and alterations in markers of autophagy (LC3 and p62).Results VillinCre;Imp1floxed mice exhibit Paneth cell mislocalization and altered morphology. Furthermore, VillinCre;Imp1floxed mice exhibit increased LC3+ puncta and decreased p62 expression, representing up‐regulation in autophagic flux.Conclusions Our data suggest that IMP1 may mediate intestinal homeostasis through a novel role in Paneth cells. The intersection of Paneth cell function and autophagy pathway components is an emerging area of interest in patients with inflammatory bowel diseases. As such, Villin‐Cre;Imp1fl/fl mice provide a compelling model for elucidating this relationship.Grant Funding Source: Supported By HHMI Medical Fellowship (ETL), NIH grants (F32 DK093207‐01, RO1 DK056645‐12, UO1 DK0855