BACH2 ameliorates lung injury in LPS-induced sepsis through activation of Nrf2 signaling

To explore the function and molecular mechanism of BACH2 in septic lung injury induced by lipopolysaccharide (LPS). We established LPS-induced septic lung injury models in mice and human bronchial epithelial BEAS-2B cells. By overexpressing/knocking down BACH2 and knocking down Nrf2, combined with pathological staining, molecular biology and cell experiment techniques, we detected the levels of lung tissue injury, inflammation and pulmonary fibrosis, and verified the regulatory relationship between BACH2 and Nrf2. In the lung tissues of mice with LPS-induced septic lung injury, the expression level of BACH2 was decreased in a time-dependent pattern. Overexpression of BACH2 significantly alleviated LPS-induced pathological injury of mouse lung tissues, inhibited neutrophil infiltration, and reduced the release of inflammatory cytokines and the degree of pulmonary fibrosis. BACH2 could directly bind to the -2000 ~ -1800 bp region of the Nrf2 promoter and upregulate its expression, and knockdown of Nrf2 completely reversed the lung protective effect of BACH2. BACH2 exerts anti-inflammatory and anti-fibrotic effects by directly binding to and activating the Nrf2 signaling pathway, thereby ameliorating LPS-induced septic lung injury. The BACH2/Nrf2 axis may serve as a candidate molecular target for further preclinical research on septic lung injury treatment.

The online version contains supplementary material available at https://doi.org/10.1007/s10616-026-01024-5.