Transcription factor CEBPA suppresses sepsis induced lung injury by activating SIRT4 transcription

This study aimed to investigate the roles of the transcription factor CEBPA and the sirtuin family protein SIRT4 in sepsis-induced acute lung injury (ALI) through both cell-based experiments and animal models. Following LPS or sepsis treatment, both CEBPA and SIRT4 levels were significantly elevated, with a strong correlation observed between these proteins across various samples. Overexpression of CEBPA or SIRT4 mitigated LPS-induced damage, promoting cell survival, reducing apoptosis, and attenuating lung inflammation and injury. In mouse models of ALI, increased expression of CEBPA and SIRT4 substantially alleviated lung injury and inflammation, whereas silencing these genes exacerbated the condition. Further analysis revealed that CEBPA directly binds to the SIRT4 promoter, thereby enhancing SIRT4 protein expression, which in turn amplifies their protective effects. This study is the first to establish a functional link between CEBPA and SIRT4 in ALI, providing novel insights for the development of therapeutic strategies targeting inflammatory diseases.