Open AccessmiR-146a Attenuates Sepsis-Induced Myocardial Dysfunction by Suppressing IRAK1 and TRAF6 via Targeting ErbB4 Expression
Author(s) -
Rui An,
Jianxin Feng,
Cong Xi,
Jian Xu,
Lichao Sun
Publication year - 2018
Publication title -
oxidative medicine and cellular longevity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.494
H-Index - 93
eISSN - 1942-0900
pISSN - 1942-0994
DOI - 10.1155/2018/7163057
Subject(s) - proinflammatory cytokine , sepsis , lipopolysaccharide , apoptosis , nf κb , inflammation , western blot , cancer research , cytokine , microrna , tumor necrosis factor alpha , innate immune system , medicine , immunology , pharmacology , chemistry , immune system , gene , biochemistry
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.