| 著者 |
Chatterji P, Williams PA, Whelan KA, Samper FC, Andres SF, Simon LA, Parham LR, Mizuno R, Lundsmith ET, Lee DS, Liang S, Wijeratne HS, Marti S, Chau L, Giroux V, Wilkins BJ, Wu GD, Shah P, Tartaglia GG, Hamilton KE.
|
| 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 (Imp1Δ
IEC
) 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 Imp1Δ
IEC
mice exhibit enhanced recovery following dextran sodium sulfate (DSS)-mediated colonic injury. Imp1Δ
IEC
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 Imp1Δ
IEC
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.
|
