miR‐146a Attenuates Sepsis‐Induced Myocardial Dysfunction by Suppressing IRAK1 and TRAF6 via Targeting ErbB4 Expression

Myocardial dysfunction is a major manifestation of sepsis and closely associated with the increased mortality. MicroRNA‐146 is one of the most important microRNAs identified as a potent negative regulator in innate immune and inflammatory responses induced by lipopolysaccharide (LPS). We aimed to identify the role and potential regulatory mechanism of miR‐146a in sepsis‐induced cardiac dysfunction with the induction of ErbB4 signaling. H9C2 cells were treated with LPS to induce sepsis, and miR‐146a overexpression significantly increased the cell viability, reduced the apoptosis and ROS level, and attenuated the release of proinflammatory cytokines including TNF‐ α and IL‐1 β . Levels of ErbB4, p‐NF‐ κ B, NF‐ κ B, TRAF6, IRAK1, caspase 3, Bcl‐2, and Bax were measured by Western blot. The overexpression of miR‐146a significantly increased the ErbB4 expression, decreased the expression of TRAF6, IRAK1, caspase 3, and the phosphorylation level of NF‐ κ B, and also increased the Bcl‐2/Bax ratio, suggesting the inhibition of inflammation and apoptosis. The protective effects were all abolished by the use of siErbB4. In conclusion, our results demonstrated that the overexpression of miR‐146a mitigates myocardial injury by negatively regulating NF‐ κ B activation and inflammatory cytokine production via targeting ErbB4 in LPS‐induced sepsis.