KLF13 overexpression protects sepsis-induced myocardial injury and LPS-induced cellular inflammation and apoptosis

Sepsis remains a worldwide public health problem. This study aims to explore the role and mechanism of transcriptional factors (TFs) in sepsis-induced myocardial injury. Firstly, TF KLF13 was selected to explore its role in sepsis-induced myocardial injury. The CLP-induced sepsis mouse model was established and the septic mice were examined for histopathological changes using H&E staining. KLF13 expression in septic mouse heart and LPS-induced cellular inflammation model was detected. Pro-apoptotic cleaved-caspase3/caspase3 and Bax levels and anti-apoptotic Bcl2 level, inflammatory cytokines (IL-1 beta, TNF-alpha, IL-8 and MCP-1) production and I kappa B-alpha protein level and p65 phosphorylation in septic mice and LPS-induced cells were detected to evaluate cardiomyocyte apoptosis, inflammatory response and NF-kappa B pathway activation. KLF13 was overexpressed in vivo and in vitro to explore its specific effect on sepsis-induced myocardial injury. The septic mice showed significant oedema, disordered myofilament arrangement and degradation and necrosis to varying degrees in myocardial cells. KLF13 was downregulated in the septic mouse heart and LPS-induced cellular inflammation model. Septic heart and LPS-induced cell model showed abnormally increased cardiomyocyte apoptosis (increased cleaved-caspase3/caspase and Bax protein levels and decreased Bcl2 level), elevated inflammation (increased production of inflammatory cytokines) and the activated NF-kappa B pathway (increased p65 phosphorylation and decreased I kappa B-alpha protein level). KLF13 overexpression notably ameliorated sepsis-induced myocardial injury in vivo and in vitro. KLF13 overexpression protected against sepsis-induced myocardial injury and LPS-induced cellular inflammation and apoptosis via inhibiting the inflammatory pathways (especially the NF-kappa B signalling) and cardiomyocyte apoptosis.