Xu Yang, Guilin Li, Pengbo Lou, Mingxin Zhang, Kai Yao, Jintao Xiao, Yiqian Chen, Jiuzhi Xu, Shengyuan Tian, Min Deng, Yuwei Pan, Mengzhen Li, Xi Wu, Ruiqi Liu, Xiaojing Shi, Yuhua Tian, Lu Yu, Hao Ke, Baowei Jiao, Yingzi Cong, Maksim V Plikus, Xiaowei Liu, Zhengquan Yu, Cong Lv
Oxidative stress, which can be activated by a variety of environmental risk factors, has been implicated as an important pathogenic factor for inflammatory bowel disease (IBD). However, how oxidative stress drives IBD onset remains elusive. Here, we found that oxidative stress was strongly activated in inflamed tissues from both ulcerative colitis patients and Crohn's disease patients, and it caused nuclear-to-cytosolic TDP-43 transport and a reduction in the TDP-43 protein level. To investigate the function of TDP-43 in IBD, we inducibly deleted exons 2 to 3 of Tardbp (encoding Tdp-43) in mouse intestinal epithelium, which disrupted its nuclear localization and RNA-processing function...
January 2, 2024: Proceedings of the National Academy of Sciences of the United States of America