MRNA‐binding protein IMP1 is a novel regulator of autophagy following intestinal irradiation injury

Abstract

BackgroundPost‐transcriptional regulation of intestinal homeostasis via mRNA‐binding proteins, including Igf2 mRNA‐binding protein 1 (IMP1), is an area of emerging interest. Imp1‐null mice exhibit severe intestinal growth defects, yet Imp1 deletion in intestinal epithelium (Imp1ΔIEC) reveals minimal phenotype. Imp1 expression is significantly increased in intestinal stem/progenitor cells post‐irradiation, and new data indicate that Imp1ΔIEC mice exhibit increased baseline autophagy. We hypothesized that Imp1 is essential for intestinal response to irradiation, possibly via modulation of autophagy.MethodsWe treated Imp1ΔIEC and control mice with 12Gy irradiation and evaluated small intestine 96 hours later. Epithelia were evaluated for changes in autophagy via western blot and FACS. Enteroids plated from crypts of Imp1ΔIEC and control mice evaluated stem cell growth.ResultsAutophagy is up‐regulated in control mice following irradiation; however, Imp1ΔIEC mice exhibit repressed autophagy. In control mice, irradiation increases the proportion of spheres (non‐differentiated) to budding enteroids (differentiated), reflecting stem cell expansion. Intriguingly, irradiated Imp1ΔIEC mice show a further increase in sphere‐like enteroids, indicating that Imp1 may function to modulate stemness/differentiation following injury.ConclusionsOur data suggest that Imp1 may regulate autophagy in response to irradiation in the intestine, representing a novel paradigm by which autophagy may influence stemness in intestinal homeostasis.