Abstract
Myocardial dysfunction is a major cause of death in sepsis. MicroRNA-146b (miR-146b) has been reported to be related to myocardial disease. However, the role of miR-146b in sepsis as well as myocardial injury is still unclear. Septic cardiac dysfunction in mice was induced by cecal ligation and puncture (CLP) and miR-146b was found increased significantly in the myocardium tissue of CLP mice. It was found that up-regulation of miR-146b by agomiR injection suppressed expression of IL-1β in mice as well as myocardium apoptosis in CLP mice. However, suppression of miR-146b by antagomiR injection had inverse effects. Notch1 was identified as a target gene of miR-146b by bioinformatics analysis. And it was verified that in cardiomyocytes, the decrease of miR146b led to increase of both the mRNA and protein level of Notch1 and vice versa. In septic mice serum stimulated cardiomyocytes, up-regulation of miR-146b decreased the level of Notch1 and Hes1. The knockout of Notch1 in transgenic mice showed that the deficiency of Notch1 improved myocardial injury induced by CLP operation. The apoptosis of cardiomyocytes was relieved and the expression of IL-1β was decreased. In conclusion, miR-146b targets to Notch1 and protected cardiomyocytes against inflammation and apoptosis.
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Acknowledgements
The authors thank Experimental Animal Center of The Fourth Military Medical University for providing the myocardium specific Notch1-/- mice and wild-type littermates.
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XW and YY designed the project. XW performed the experiments, and analyzed data. YY wrote the manuscript. XW and YY approved the final submission.
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10735_2018_9781_MOESM1_ESM.tif
Supplementary Figure. Chemically modified sense RNAs (miR-146b agomiR) and antisense RNA (miR-146b antagomiR) were synthesized by Qiagen. Mouse cardiomyocytes were transfected with antagomiR or agomiRs using HiPerFect Transfection Reagent (Qiagen). The cells were incubated with the transfection complexes for 48h. Then the miRNA levels were tested by qRT-PCR. (TIF 160 KB)
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Wang, X., Yu, Y. MiR-146b protect against sepsis induced mice myocardial injury through inhibition of Notch1. J Mol Hist 49, 411–417 (2018). https://doi.org/10.1007/s10735-018-9781-4
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DOI: https://doi.org/10.1007/s10735-018-9781-4