Related Experiment Video
Updated: Jun 28, 2025
Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics
Published on: March 15, 2024
Knockdown of KBTBD7 attenuates septic lung injury by inhibiting ferroptosis and improving mitochondrial dysfunction
Xiang Li1, Zhao Lin1, ShiYu Xu1
1Department of Critical Care Medicine, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, Jiangsu, 211100, China.
Abstract:
Lung injury in sepsis is caused by an excessive inflammatory response caused by the entry of pathogenic microorganisms into the body. It is also accompanied by the production of large amounts of ROS. Ferroptosis and mitochondrial dysfunction have also been shown to be related to sepsis. Finding suitable sepsis therapeutic targets is crucial for sepsis research. BTB domain-containing protein 7 (KBTBD7) is involved in regulating inflammatory responses, but its role and mechanism in the treatment of septic lung injury are still unclear. In this study, we evaluated the role and related mechanisms of KBTBD7 in septic lung injury. In in vitro studies, we established an in vitro model by inducing human alveolar epithelial cells with lipopolysaccharide (LPS) and found that KBTBD7 was highly expressed in the in vitro model. KBTBD7 knockdown could reduce the inflammatory response by inhibiting the secretion of pro-inflammatory factors and inhibit the production of ROS, ferroptosis and mitochondrial dysfunction. Mechanistic studies show that KBTBD7 interacts with FOXA1, promotes FOXA1 expression, and indirectly inhibits SLC7A11 transcription. In vivo studies have shown that knocking down KBTBD7 improves lung tissue damage in septic lung injury mice, inhibits inflammatory factors, ROS production and ferroptosis. Taken together, knockdown of KBTBD7 shows an alleviating effect on septic lung injury in vitro and in vivo, providing a potential therapeutic target for the treatment of septic lung injury.
Insights
Knocking down BTB domain-containing protein 7 (KBTBD7) alleviates septic lung injury by reducing inflammation, reactive oxygen species (ROS), and ferroptosis. This study identifies KBTBD7 as a potential therapeutic target for sepsis-induced lung damage.
Area of Science:
- Biomedical Research
- Molecular Biology
- Pathology
Background:
- Sepsis-induced lung injury involves excessive inflammation, reactive oxygen species (ROS), ferroptosis, and mitochondrial dysfunction.
- The role of BTB domain-containing protein 7 (KBTBD7) in septic lung injury remains largely unknown.
- Identifying novel therapeutic targets is critical for managing sepsis complications.
Purpose of the Study:
- To investigate the role and underlying mechanisms of KBTBD7 in septic lung injury.
- To evaluate the therapeutic potential of targeting KBTBD7 for septic lung injury.
Main Methods:
- In vitro: Human alveolar epithelial cells stimulated with lipopolysaccharide (LPS) to model septic lung injury.
- In vivo: Mouse model of septic lung injury.
- KBTBD7 knockdown was performed using in vitro and in vivo approaches.
- Mechanistic studies involved assessing inflammatory factors, ROS production, ferroptosis, mitochondrial dysfunction, and KBTBD7-FOXA1-SLC7A11 interactions.
Main Results:
- KBTBD7 expression was upregulated in an in vitro model of septic lung injury.
- KBTBD7 knockdown reduced inflammation, ROS production, ferroptosis, and mitochondrial dysfunction in vitro.
- KBTBD7 interacts with FOXA1, promoting its expression and inhibiting SLC7A11 transcription.
- KBTBD7 knockdown ameliorated lung tissue damage, inflammation, ROS, and ferroptosis in vivo.
Conclusions:
- KBTBD7 knockdown demonstrates a protective effect against septic lung injury.
- KBTBD7 inhibition mitigates key pathological features of sepsis-induced lung damage.
- KBTBD7 represents a promising therapeutic target for treating septic lung injury.
