期刊
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
卷 9, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fcell.2021.650666
关键词
miR-22; autophagy; apoptosis; septic cardiomyopathy; sirt1
资金
- National Natural Science Foundation of China [81900338]
- Shaanxi Natural Science Basic Research Program [2020JQ455]
- Eagle Program from The Fourth Military Medical University [015210]
In septic cardiomyopathy, miR-22 plays an important role by promoting autophagy and reducing apoptosis. Inhibiting miR-22 can exert a cardioprotective effect, potentially becoming a new strategy for treating septic cardiomyopathy.
High morbidity and mortality are the most typical characteristics of septic cardiomyopathy. We aimed to reveal the role of miR-22 in septic cardiomyopathy and to explore the underlying mechanisms. miR-22 cardiac-specific knockout (miR-22(cKO)) mice and miR-22 cardiac-specific transgenic (miR-22(cOE)) mice were subjected to a cecal ligation and puncture (CLP) operation, while a sham operation was used in the control group. The echocardiogram results suggested that miR-22(cKO) CLP mice cardiac dysfunction was alleviated. The serum LDH and CK-MB were reduced in the miR-22(cKO) CLP mice. As expected, there was reduced apoptosis, increased autophagy and alleviated mitochondrial dysfunction in the miR-22(cKO) CLP mice, while it had contrary role in the miR-22(cOE) group. Inhibiting miR-22 promoted autophagy by increasing the LC3II/GAPDH ratio and decreasing the p62 level. Additionally, culturing primary cardiomyocytes with lipopolysaccharide (LPS) simulated sepsis-induced cardiomyopathy in vitro. Inhibiting miR-22 promoted autophagic flux confirmed by an increased LC3II/GAPDH ratio and reduced p62 protein level under bafilomycin A1 conditions. Knocking out miR-22 may exert a cardioprotective effect on sepsis by increasing autophagy and decreasing apoptosis via sirt1. Our results revealed that targeting miR-22 may become a new strategy for septic cardiomyopathy treatment.
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