Work

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

Year: 2025

Type: article

Abstract: BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Source: BMC Cardiovascular Disorders

DOI: 10.1186/s12872-025-05450-9

Authors: Mei Yang, Wen Pan, Qin Chen, Yong Cheng, Guoji Zhu

Institutions: Soochow University, Children's Hospital of Suzhou University

Language: English

Topic: Sepsis Diagnosis and Treatment

Subfield: Epidemiology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,090