A study on the mechanism of IGFBP-3 affecting autophagy to partially protect against inflammatory damage in inflammatory bowel disease.

Given the vital role of IGF-1 binding protein-3 (IGFBP-3) in inflammatory bowel disease (IBD), this study analyzed the mechanisms of IGFBP-3 affecting autophagy and inflammatory damage in IBD. IBD was induced in mice using 2,4,6-trinitrobenzenesulfonic acid. Mice were then treated with IGFBP-3 overexpression lentivirus, a Wnt/β-catenin pathway activator (HLY78), and an autophagy inhibitor (chloroquine). Body weight changes and disease activity index (DAI) scores within 7 days, as well as colon length and colon macroscopic visible damage scores, were recorded. Colon tissue morphology was observed using HE staining, with histological damage scored. ELISA was performed to determine tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-10 levels, and RT-qPCR and Western blot to measure IGFBP-3, Wnt, β-catenin, Axin2, LC3B II/I, and p62 levels in colon tissues. IBD mice exhibited decreased body weight and increased DAI scores within 7 days, along with a shortened colon length, increased macroscopic visible damage and histological damage scores, up-regulated TNF-α and IL-6 levels, and down-regulated IL-10 and IGFBP-3 levels in colon tissues. IGFBP-3 overexpression blocked the Wnt/β-catenin pathway and contributed to partial protection against inflammatory damage in colon tissues as well as promotion of autophagy in IBD mice. Inhibition of autophagy partially averted the protective effect of IGFBP-3 overexpression on inflammatory damage in IBD mice. IGFBP-3 disrupts the Wnt/β-catenin pathway and promotes autophagy, thereby partially protecting against inflammatory damage in IBD mice.