Klotho downregulation contributes to myocardial damage of cardiorenal syndrome in sepsis.

Klotho is a type of single-pass transmembrane protein that is important for the proper function of numerous organs. The aim of the present study was to investigate the role of Klotho in sepsis-associated myocardial damage. In the present study, reverse transcription-quantitative PCR, western blotting and ELISA were conducted to examine the expression levels of function genes, and flow cytometry was performed to detect cell apoptosis and reactive oxygen species. The present study demonstrated that Klotho expression was significantly downregulated in septic mice and that the myocardial function of septic mice improved after treatment with exogenous Klotho protein. It further demonstrated that indoxyl sulfate inhibited the expression of Klotho protein. In addition, decreased Klotho protein further led to activation of the reactive oxygen species-p38 mitogen-activated protein kinase signaling pathway, finally resulting in myocardial damage. In conclusion, Klotho protein may be a key regulator in the myocardial damage of cardiorenal syndrome in sepsis. It also has a potential to be a therapeutic target for sepsis-associated myocardial damage in the future.