Nicotinamide riboside attenuates radiation-induced intestinal injury by suppressing gasdermin E-mediated pyroptosis in intestinal epithelial cells

作者：Qian Zhou, Xiaoyang Li, Xinlong Lin, Binhai Shen, Weifeng Huang, Yin Zhang, Yinmu Li, Yuyi Yang, Hongbin Liu, Wendi Zhang, Xinmei Zhao, Weiguang Qiao, Yangyang Liu, Gao Tan, Fachao Zhi · 发表于：Journal of Translational Medicine · 年份：2025 · DOI：10.1186/s12967-025-07012-1 · 被引用次数：2 · 研究领域：Inflammasome and immune disorders、Sirtuins and Resveratrol in Medicine、PARP inhibition in cancer therapy

Radiation-induced intestinal injury (IR) is a common complication in patients with colorectal cancer (CRC) after radiotherapy. Currently, the search for effective treatments has become an urgent priority. Nicotinamide riboside (NR), the precursor of vitamin B3 derivative and NAD (+), was enriched in IR after treatment with commensal Bacteroides fragilis , suggesting that NR may perform a protective role. However, the specific role of NR in IR remains unclear. In this study, we investigated the therapeutic effects of NR on IR. C57BL/6J, Gsdme ΔIEC (lacking GSDME in intestinal epithelial cells, IECs), and wild-type littermates were treated with NR after abdominal radiation exposure at 10 Gy. The small intestinal crypt-derived organoids and cell lines FHC, NCM460, and IEC-6 were irradiated with or without administration of the SIRT1 inhibitor EX527 under NR stimulation. A series of assays were subsequently carried out to explore the therapeutic effects, the degree of IECs repair, and the underlying mechanism. NR significantly ameliorated IR in mice, as evidenced by reduced weight loss, shortened small intestinal and colonic length, improved histological associated index, and restored the intestinal flora, which increased the relative abundance of the commensal Muribaculaceae , and decreased the relative abundance of Escherichia_coli . Additionally, NR increased goblet cell density, increased crypt length, promoted Ki-67 and ZO-1 expression, reduced reactive oxygen species (ROS) ...