MicroRNA-223-3p modulates dendritic cell function and ameliorates experimental autoimmune myocarditis by targeting the NLRP3 inflammasome

Chen, Liangqi; Hou, Xinyu; Zhang, Maomao; Yang, Zheng; Zheng, Xianghui; Yang, Qingyuan; Li, Jing; Gu, Nan; Zhang, Min; Sun, Yong; Wu, Jiarui; Yu, Bo

doi:10.1016/j.molimm.2019.10.027

Cited by 45 publications

(36 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Myocarditis is a disease featured by the existence of inflammatory infiltrates in cardiac tissue, which is the leading cause of acute cardiac failure, sudden death and dilated cardiomyopathy in children and young people [1][2][3]. The short-term prognosis of acute myocarditis is generally well, but varies greatly by etiology.…”

Section: Introductionmentioning

confidence: 99%

Myc is involved in Genistein protecting against LPS-induced myocarditis in vitro through mediating MAPK/JNK signaling pathway

Huang

Zhang

et al. 2020

Bioscience Reports

View full text Add to dashboard Cite

Background: Genistein is widely used as a pharmacological compound as well as a food additive. However, the pharmaceutical effects of Genistein on myocarditis and its potential mechanisms have not been studied in detail. Methods: H9c2 cells were continuously stimulated by lipopolysaccharide (LPS) for 12 h to simulate the in vitro model of myocarditis injury. DrugBank, String, and GEO dataset were used to investigate specific genes that interacting with Genistein. KEGG and GO enrichment analysis were employed to explore Myc-related signaling pathways. Biological behaviors of H9c2 cells were observed with the support of cell counting kit-8, MTT and flow cytometry. Expression levels of cytokines including TNF-α and ILs were evaluated by enzyme-linked immunosorbent assay. Western blot was applied to detect the expression of Myc and MAPK pathway related proteins. Results: Genistein alleviated the damage of H9c2 cells subjected to LPS from the perspective of elevating cells growth ability, and inhibiting cells apoptosis and inflammatory response. Through bioinformatics analysis, we identified Myc as the potential target of Genistein in myocarditis, and MAPK as the signaling pathway. Significantly, Myc was highly up-regulated in myocarditis samples. More importantly, by performing biological experiments, we discovered that Genistein relieved H9c2 cells apoptosis and inflammatory reaction which caused by LPS stimulation through inhibiting Myc expression. Additionally, the marked augmentation of p-P38 MAPK and p-JNK expression in LPS-induced cardiomyocyte model were blocked by Genistein and si-Myc. Conclusions: Our research revealed that Myc mediated the protective effects of Genistein on H9c2 cells damage caused by LPS partly through modulation of MAPK/JNK signaling pathway.

show abstract

Section: Introductionmentioning

confidence: 99%

Myc is involved in Genistein protecting against LPS-induced myocarditis in vitro through mediating MAPK/JNK signaling pathway

Huang

Zhang

et al. 2020

Bioscience Reports

View full text Add to dashboard Cite

show abstract

“…Previous studies have reported that MEG3 can bind to miR‐223 and inhibit the expression of miR‐223 expression and that miR‐223 is down‐regulated in mice with myocarditis 15,16,32 . Therefore, we have been suggested that MEG3 might bind to miR‐223 to orchestrate VMC development.…”

Section: Resultsmentioning

confidence: 90%

“…IHC showed that over‐expressed miR‐223 or down‐regulated TRAF6 resulted in significantly decreased TRAF6 expression (Figure 4F). miR‐223 has previously been shown to decrease the expression of NLRP3 inflammatory corpuscles in the autoimmune myocarditis model, thus promoting the differentiation of dendritic cells (DCs) into tolerant DC phenotypes 32 . Meanwhile, following miR‐223 up‐regulation or TRAF6 down‐regulation, expression of NLRP3 inflammasome‐related components (NLRP3, ASC and Caspase‐1) was reduced (Figure 4G), mouse body weight was elevated (Figure 4H), survival rate was increased (Figure 4I), myocarditis was inhibited in mice (Figure 4J,K), and LVEF and LVFS rose in VMC mice (Figure 4L,M).…”

Section: Resultsmentioning

confidence: 99%

“…For example, overexpression of miR‐1 can promote VMC progression via Cx43 suppression 44 . miR‐223‐3p alleviated experimental autoimmune myocarditis by repressing NLRP3 inflammasome expression and promoting the polarization of DCs towards a tolerant DC phenotype 32 . miR‐223 is a circulating miRNA that involves in the inflammatory process of hepatitis and other chronic diseases 45 .…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Long non‐coding RNA MEG3 inhibits M2 macrophage polarization by activating TRAF6 via microRNA‐223 down‐regulation in viral myocarditis

Xue

Zhang

Zheng

et al. 2020

J Cellular Molecular Medi

View full text Add to dashboard Cite

show abstract

“…In mice with EAM, miR-223-3p ameliorated inflammatory response by targeting pyrin domain-containing-3 (NLRP3) inflammasome which is a multiprotein complex and sensor in innate immune cells (140). miR-21, miR-146b, and miR-155 are consistently up-regulated in patients with acute VMC (141), and mice with myocarditis induced by CVB3 or T. cruzi (112).…”

Section: Immune Status-related Mirnasmentioning

confidence: 99%

Dysregulated CD4+ T Cells and microRNAs in Myocarditis

Wang

Han

2020

Front. Immunol.

View full text Add to dashboard Cite

Myocarditis is a polymorphic disease complicated with indeterminate etiology and pathogenesis, and represents one of the most challenging clinical problems lacking specific diagnosis and effective therapy. It is caused by a complex interplay of environmental and genetic factors, and causal links between dysregulated microribonucleic acids (miRNAs) and myocarditis have also been supported by recent epigenetic researches. Both dysregulated CD4+ T cells and miRNAs play critical roles in the pathogenesis of myocarditis, and the classic triphasic model of its pathogenesis consists of the acute infectious, subacute immune, and recovery/chronic myopathic phase. CD4+ T cells are key pathogenic factors underlying the development and progression of myocarditis, and the effector and regulatory subsets, respectively, promote and inhibit autoimmune responses. Furthermore, the reciprocal interplay of these subsets influences the pathogenesis as well. Dysregulated miRNAs along with their mRNA and protein targets have been identified in heart biopsies (intracellular miRNAs) and body fluids (circulating miRNAs) during myocarditis. These miRNAs show phase-dependent changes, and correlate with viral infection, immune status, fibrosis, destruction of cardiomyocytes, arrhythmias, cardiac functions, and outcomes. Thus, miRNAs are promising diagnostic markers and therapeutic targets in myocarditis. In this review, we review myocarditis with an emphasis on its pathogenesis, and present a summary of current knowledge of dysregulated CD4+ T cells and miRNAs in myocarditis.

show abstract

MicroRNA-223-3p modulates dendritic cell function and ameliorates experimental autoimmune myocarditis by targeting the NLRP3 inflammasome

Cited by 45 publications

References 51 publications

Myc is involved in Genistein protecting against LPS-induced myocarditis in vitro through mediating MAPK/JNK signaling pathway

Myc is involved in Genistein protecting against LPS-induced myocarditis in vitro through mediating MAPK/JNK signaling pathway

Long non‐coding RNA MEG3 inhibits M2 macrophage polarization by activating TRAF6 via microRNA‐223 down‐regulation in viral myocarditis

Dysregulated CD4+ T Cells and microRNAs in Myocarditis

Contact Info

Product

Resources

About