Knockdown of JunB alleviates LPS-induced H9C2 cardiomyocyte injury and sepsis-induced myocardial injury by activating the PI3K/Akt/mTOR signaling pathway

JunB expression found to be upregulated in sepsis-induced myocardial injury (SIMI) tissue samples, yet its role in this disease remains unexplored‌. This study aimed to investigate the role and underlying mechanism of JunB in SIMI. In vitro and in vivo SIMI models were established by stimulating H9C2 cardiomyocytes with lipopolysaccharide (LPS) and inducing sepsis via cecal ligation and puncture (CLP) in mice, respectively. In both models, JunB expression was modulated, and several key parameters were evaluated, including apoptosis, levels of inflammatory cytokines (IL-6 and TNF-α), oxidative stress, ferroptosis, and endoplasmic reticulum (ER) stress. Additionally, the activation of PI3K/Akt/mTOR signaling pathway was examined. To confirm the mechanism of JunB, a PI3K/Akt-specific inhibitor, LY294002, was applied in the cell model. JunB expression was elevated in both SIMI models. In vitro, JunB downregulation significantly increased cell viability, SOD activity, and GPX4 expression, while it decreased IL-6 and TNF-α levels, reduced apoptosis, ROS accumulation, MDA content, and ATF6 expression. In contrast, JunB upregulation produced the opposite effects. In vivo, downregulation of JunB reduced serum levels of myocardial injury markers (CK-MB and cTnT), improved myocardial damage, and decreased myocardial inflammation, apoptosis, oxidative stress, ferroptosis, and ER stress. JunB knockdown activated the PI3K/Akt/mTOR pathway in both models. LY294002 treatment reversed the protective effects of JunB silencing on LPS-induced cell injury. Knockdown of JunB alleviates sepsis-induced myocardial inflammation, apoptosis, oxidative stress, ferroptosis, and ER stress by activating the PI3K/Akt/mTOR signaling pathway. This suggests that JunB may be a potent therapeutic target for SIMI.