Radiation-induced gastrointestinal syndrome is alleviated in NDRG2-deficient mice.

Background Radiation-induced gastrointestinal syndrome (GIS) often occurs after therapeutic or accidental exposure to high doses of radiation. Unfortunately, there are still no effective medical treatments for GIS. N-Myc downstream regulated gene 2 (NDRG2), is a tumor suppressor gene and promotes cell apoptosis and differentiation. The aim of our study was to identify the role of NDRG2 in the progression of GIS and explore the potential mechanism. Methods We generated Ndrg2ΔG mice, lacking NDRG2 specifically in the intestinal epithelium. Survival analysis was performed to validate the effect of NDRG2 on GIS, and other common indicators (body weight loss and diarrhea) were used for the assessment of GIS. Enzyme-linked immunosorbent assay (ELISA) and reverse transcription-polymerase chain reaction (RT-PCR) were conducted to obtain the expression of pro-inflammatory interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha (TNF-α). TUNNEL and western blotting were further adopted to determine the relationship between NDRG2 and apoptosis. Finally, we performed histology and immunohistochemistry assays to explore the morphological alternations and changes of proliferation-related molecules, including Ki-67 and proliferating cell nuclear antigen (PCNA). Results We found that after 8 gray of total body ɤ-irradiation (TBI), the deletion of NDRG2 in the intestine revealed longer survival time, considerably milder symptoms of GIS, and milder damage to jejunal tissue, compared with the WT mice. Moreover, the Ndrg2ΔG mice significantly inhibited the expression of pro-inflammatory IL-1β, IL-6, and TNF-α, which were typically increased by irradiation. Apoptosis of the epithelial cells in the Ndrg2ΔG mice was significantly milder while the ratio of proliferation cells was larger in the epithelium of mice 8 days after TBI when compared with the WT mice. Conclusions These findings all indicated that NDRG2 deficiency in the intestine protects mice against radiation-induced GIS mainly through promoting proliferation and suppressing apoptosis of epithelial cells.