Jiahui Ni, Lijie Zhang, Guize Feng, Weilian Bao, Yirui Wang, Yuran Huang, Tongqing Chen, Jieli Chen, Xinyue Cao, Keyuan You, Sheng Tan, Thomas Efferth, Hong Li, Bo Li, Xiaoyan Shen, Yan You
The damage of integrated epithelial epithelium is a key pathogenic factor and closely associated with the recurrence of ulcerative colitis (UC). Here, we reported that vanillic acid (VA) exerted potent therapeutic effects on DSS-induced colitis by restoring intestinal epithelium homeostasis via the inhibition of ferroptosis. By the CETSA assay and DARTS assay, we identified carbonic anhydrase IX (CAIX, CA9) as the direct target of VA. The binding of VA to CA9 causes insulin-induced gene-2 (INSIG2) to interact with stromal interaction molecule 1 (STIM1), rather than SREBP cleavage-activating protein (SCAP), leading to the translocation of SCAP-SREBP1 from the endoplasmic reticulum (ER) to the Golgi apparatus for cleavage into mature SREBP1...
March 2, 2024: Pharmacological Research: the Official Journal of the Italian Pharmacological Society