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IMP1 loss in intestinal epithelial cells promotes altered Paneth cell morphology and autophagy defects (899.2)
Author(s) -
Lundsmith Emma,
Hamilton Kathryn,
Noubissi Felicite,
Hahn Christopher,
Spiegelman Vladimir,
Rustgi Anil
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.899.2
Subject(s) - paneth cell , microbiology and biotechnology , autophagy , stem cell , homeostasis , embryonic stem cell , biology , intestinal epithelium , chemistry , epithelium , small intestine , endocrinology , biochemistry , gene , genetics , apoptosis
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;Imp1 floxed mice) for Paneth cell morphology (lysozyme), and alterations in markers of autophagy (LC3 and p62). Results VillinCre;Imp1 floxed mice exhibit Paneth cell mislocalization and altered morphology. Furthermore, VillinCre;Imp1 floxed 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;Imp1 fl/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