Erbin deficiency exacerbates sepsis‑induced liver injury through mitochondrial ROS/NLRP3‑mediated inflammatory responses

Sepsis‑induced liver injury (SLI) is a life‑threatening complication of sepsis characterized by microcirculatory dysfunction, oxidative stress, excessive inflammation, and immune dysregulation. However, the role of ErbB2 interacting protein (Erbin) in SLI remains unclear. In the present study, the functional role and underlying mechanism of Erbin were investigated in a cecal ligation and puncture (CLP)‑induced mouse model of SLI using wild‑type and Erbin‑knockout (Erbin‑/‑) mice, together with lipopolysaccharide (LPS)/adenosine triphosphate (ATP)‑stimulated bone marrow‑derived macrophages (BMDMs). Liver histopathology, mitochondrial ultrastructure, oxidative stress, inflammatory cytokine production, and pyroptosis‑related signaling were assessed using H&E staining, transmission electron microscopy, biochemical assays, ELISA, quantitative PCR, immunohistochemistry, and western blotting. Erbin deficiency markedly aggravated CLP‑induced liver injury, as evidenced by more severe histopathological damage, mitochondrial disruption, oxidative stress, NOD‑like receptor family pyrin domain containing 3 (NLRP3) inflammasome activation, and pro‑inflammatory cytokine production. Mechanistically, Erbin deficiency promoted mitochondrial ROS accumulation, enhanced thioredoxin‑interacting protein (TXNIP)‑NLRP3 interactions, and intensified inflammatory activation and pyroptotic responses. Mitochondrial ROS scavenging with MitoQ substantially attenuated the pro‑pyroptotic and pro‑inflammatory effects of Erbin deficiency in LPS/ATP‑stimulated BMDMs. Collectively, these findings identify Erbin as an endogenous protective regulator that mitigates SLI by suppressing mitochondrial ROS‑driven TXNIP/NLRP3 inflammasome activation and inflammatory responses.