@article{9bf5a9e836544a7d911708ffd4e9de88,
title = "Posttranscriptional regulation of colonic epithelial repair by RNA binding protein IMP1/IGF2BP1",
abstract = "RNA binding proteins, including IMP1/IGF2BP1, are essential regulators of intestinal development and cancer. Imp1 hypomorphic mice exhibit gastrointestinal growth defects, yet the specific role for IMP1 in colon epithelial repair is unclear. Our prior work revealed that intestinal epithelial cell-specific Imp1 deletion (Imp1ΔIEC) was associated with better regeneration in mice after irradiation. Here, we report increased IMP1 expression in patients with Crohn's disease and ulcerative colitis. We demonstrate that Imp1ΔIEC mice exhibit enhanced recovery following dextran sodium sulfate (DSS)-mediated colonic injury. Imp1ΔIEC mice exhibit Paneth cell granule changes, increased autophagy flux, and upregulation of Atg5. In silico and biochemical analyses revealed direct binding of IMP1 to MAP1LC3B, ATG3, and ATG5 transcripts. Genetic deletion of essential autophagy gene Atg7 in Imp1ΔIEC mice revealed increased sensitivity of double-mutant mice to colonic injury compared to control or Atg7 single mutant mice, suggesting a compensatory relationship between Imp1 and the autophagy pathway. The present study defines a novel interplay between IMP1 and autophagy, where IMP1 may be transiently induced during damage to modulate colonic epithelial cell responses to damage.",
keywords = "IGF2BP1, IMP1, RNA binding protein, colonic repair, inflammatory bowel disease",
author = "Priya Chatterji and Williams, {Patrick A.} and Whelan, {Kelly A.} and Samper, {Fernando C.} and Andres, {Sarah F.} and Simon, {Lauren A.} and Parham, {Louis R.} and Rei Mizuno and Lundsmith, {Emma T.} and Lee, {David S.M.} and Shun Liang and Wijeratne, {HR Sagara} and Stefanie Marti and Lillian Chau and Veronique Giroux and Wilkins, {Benjamin J.} and Wu, {Gary D.} and Premal Shah and Tartaglia, {Gian G.} and Hamilton, {Kathryn E.}",
note = "Funding Information: We wish to thank Dr. Anil K. Rustgi (UPenn) and laboratory for support, discussions, and technical input. We thank UPenn Core Facilities: Molecular Pathology and Imaging, Human and Microbial Analytic Repository, Cell Culture/iPS, Flow Cytometry, and Electron Microscopy. We thank Dr. Donita Brady (UPenn) and laboratory for technical advice. We thank also Drs. T. Stappenbeck, A. Rodriguez, P. Vedula, L. Ghanem, and Y. Barash for discussions and advice. We thank Drs. Speigelman and Noubissi for Imp1-floxed mice. Research reported in this publication was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health under Award Number UL1TR001878. NIH K01DK100485 (KEH), Crohn's and Colitis Foundation Career Development Award (KEH), NIH R03DK114463 (KEH); Institute for Translational Medicine and Therapeutics of the Perelman School of Medicine at the University of Pennsylvania (KEH); NIH P30DK050306 and its pilot grant program (KEH); start-up funds from the Children's Hospital of Philadelphia Research Institute (KEH); NIH T32CA115299-09 (SFA); NIH R01DK056645 (PC, RM, SFA); NIH K08DK099379 (BJW); European Union Seventh Framework Programme (FP7/2007-2013), through the European Research Council and RIBOMYLOME_309545 (GGT), the Spanish Ministry of Economy and Competitiveness (BFU2014-55054-P and fellowship to FCS), AGAUR (2014 SGR 00685), the Spanish Ministry of Economy and Competitiveness, Centro de Excelencia Severo Ochoa 2013–2017{\textquoteright} (SEV-2012-0208), NIH F32DK107052 (SFA), NIH K01DK103953 (KAW), NIH R03DK118304 (KAW), HHMI Medical Research Fellows Program (ETL), and Fonds de Recherche en Sant{\'e} du Qu{\'e}bec (P-Giroux-27692 and P-Giroux-31601), NIH R01GM103591 (GDW). NIH R35GM124976 (SL, HRSW, PS), NIGMS T32GM008216-29 (SWF), start-up funds from Human Genetics Institute of New Jersey and Rutgers University (SL, HRSW, PS). Funding Information: We wish to thank Dr. Anil K. Rustgi (UPenn) and laboratory for support, discussions, and technical input. We thank UPenn Core Facilities: Molecular Pathology and Imaging, Human and Microbial Analytic Repository, Cell Culture/iPS, Flow Cytometry, and Electron Microscopy. We thank Dr. Donita Brady (UPenn) and laboratory for technical advice. We thank also Drs. T. Stappenbeck, A. Rodriguez, P. Vedula, L. Ghanem, and Y. Barash for discussions and advice. We thank Drs. Speigelman and Noubissi for Imp1-floxed mice. Research reported in this publication was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health under Award Number UL1TR001878. NIH K01DK100485 (KEH), Crohn{\textquoteright}s and Colitis Foundation Career Development Award (KEH), NIH R03DK114463 (KEH); Institute for Translational Medicine and Therapeutics of the Perelman School of Medicine at the University of Pennsylvania (KEH); NIH P30DK050306 and its pilot grant program (KEH); start-up funds from the Children{\textquoteright}s Hospital of Philadelphia Research Institute (KEH); NIH T32CA115299-09 (SFA); NIH R01DK056645 (PC, RM, SFA); NIH K08DK099379 (BJW); European Union Seventh Framework Programme (FP7/2007-2013), through the European Research Council and RIBOMY-LOME_309545 (GGT), the Spanish Ministry of Economy and Competitiveness (BFU2014-55054-P and fellowship to FCS), AGAUR (2014 SGR 00685), the Spanish Ministry of Economy and Competitiveness, Centro de Excelencia Severo Ochoa 2013–2017{\textquoteright} (SEV-2012-0208), NIH F32DK107052 (SFA), NIH K01DK103953 (KAW), NIH R03DK118304 (KAW), HHMI Medical Research Fellows Program (ETL), and Fonds de Recherche en Sant{\'e} du Qu{\'e}bec (P-Giroux-27692 and P-Giroux-31601), NIH R01GM103591 (GDW). NIH R35GM124976 (SL, HRSW, PS), NIGMS T32GM008216-29 (SWF), start-up funds from Human Genetics Institute of New Jersey and Rutgers University (SL, HRSW, PS). Publisher Copyright: {\textcopyright} 2019 The Authors",
year = "2019",
month = jun,
doi = "10.15252/embr.201847074",
language = "English (US)",
volume = "20",
journal = "EMBO Reports",
issn = "1469-221X",
publisher = "Nature Publishing Group",
number = "6",
}