Objective: A growing body of evidence demonstrated that microRNAs (miRNAs) play a key role in sepsis-induced organ dysfunction. However, the mechanism of miR-361-5p in sepsis-induced myocardial injury remains to be clarified.
Methods: A mouse model of sepsis-induced myocardial injury was established using lipopolysaccharide (LPS). MiR-361-5p expression level was determined by quantitative reverse transcription-polymerase chain reaction (RT-qPCR). G protein-coupled receptor-4 (Lgr4), apoptosis-related proteins, and the Wnt signaling pathway-related proteins were determined by Western blotting. The relationship between miR-361-5p and Lgr4 was determined using dual-luciferase reporter (DLR) and RNA immunoprecipitation (RIP) assays.
Results: MiR-361-5p expression level was upregulated in the mouse model of sepsis-induced myocardial injury, while an opposite result was found for Lgr4 expression level. Knockdown of miR-361-5p protected the mouse model of sepsis-induced myocardial injury against inflammation and oxidative stress, and reduced cardiomyocyte (CM) apoptosis, which could be reversed by knockdown of Lgr4. The analysis of underlying mechanism revealed that miR-361-5p could target Lgr4 to modulate the activity of Wnt axis in CM apoptosis.
Conclusion: MiR-361-5p could aggravate myocardial injury in LPS-induced septic mice by targeting Lgr4 to inhibit the Wnt axis.
Keywords: Cardiomyopathy; Lgr4; MiR-361-5p; Sepsis.
© 2022 by the Association of Clinical Scientists, Inc.