TRIM31 promotes apoptosis via TAK1-mediated activation of NF-κB signaling in sepsis-induced myocardial dysfunction

Sepsis is a major condition caused by an overwhelming inflammatory response to an infection. Sepsis-induced myocardial dysfunction (SIMD) is a common complication in septic patients and a major predictor of morbidity and mortality. Here, we investigated the role of tripartite motif 31 (TRIM31) protein in sepsis progression <i>in vitro</i> and <i>in vivo</i>. Quantitative real-time PCR and western blot were used to detect the expression levels of relative genes and proteins. Cell proliferation and apoptosis were evaluated to determine cell viability. H&amp;E and IHC staining were performed to examine morphological and pathological changes in mice. ELISA assay was used to detect inflammatory factors. TRIM31 was upregulated in septic patients compared with normal people. TRIM31 depletion reduced LPS-induced apoptosis whereas TRIM31 overexpression-elevated LPS-induced apoptosis. Furthermore, TRIM31 interacted with and ubiquitinated transforming growth factor-β-activated kinase-1 (TAK1), resulting in TAK1 activation and subsequent induction of NF-κB signaling. Of note, <i>Trim31</i> depletion or blockade by PDTC treatment inhibited LPS-induced apoptosis <i>in vivo</i>. In conclusion, TRIM31 played an important role in SIMD by activating TAK1-mediated NF-κB signaling pathway.