MicroRNA-98 plays a critical role in experimental myocarditis

Chen, Xiao; Dong, Shu; Chen, Liang; Li, Mao-Gang; Yang, Ping‐Chang; Song, Jiangping

doi:10.1016/j.ijcard.2016.11.263

Cited by 26 publications

(24 citation statements)

References 24 publications

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“…The histology and Eo counts in the heart tissues were comparable between wild-type (WT) mice and KO mice at naive status, indicating that the Bcl2L12 KO does not alter the baseline of Eo development in the heart and does not affect the heart tissue structure. KO mice and WT mice were immunized with MyHCα to generate Mcd-like inflammation in the heart following the established procedures ( 14 ). The destructive heart tissues ( Figure 6A ), increases in Eos in the heart ( Figures 6B,C ), high inflammatory scores ( Figure 6D ), overinfiltration of mononuclear cells ( Figure 6E ), fibrosis ( Figures 6F,G ), and skewed cardiac functions, including electrocardiogram (ECG; Figure 7A ), left ventricular end-diastolic dimension (LVEDD; Figure 7B ), left ventricular ejection fraction (LVEF; Figure 7C ), left ventricular fractional shortening (FS; Figure 7D ), and isovolumic relaxation time (IVRT; Figure 7E ), were observed in immunized WT mice, but not in immunized KO mice.…”

Section: Resultsmentioning

confidence: 99%

RETRACTED: Inhibition of Bcl2L12 Attenuates Eosinophilia-Related Inflammation in the Heart

et al. 2020

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Background: The eosinophilic inflammation plays a critical role in myocarditis (Mcd); its underlying mechanism remains to be further elucidated. This study aims to investigate the role of Bcl2-like protein 12 (Bcl2L12) in inducing the defects of apoptosis in eosinophils (Eos) of the heart tissues. Methods: Human explant heart samples were collected. Eosinophilia and myocarditis (Mcd)-like inflammation were induced in the mouse heart by immunizing with murine cardiac α-myosin heavy chain (MyHCα) peptides. Results: Markedly more Eos were observed in heart tissues from patients with Mcd than those from patients with dilated cardiomyopathy. Eos isolated from Mcd hearts showed the signs of apoptosis defects. The Eo counts in the Mcd heart tissues were positively correlated with the Bcl2L12 expression in Eos isolated from the heart tissues. Exposure to interleukin 5 in the culture induced the expression of Bcl2L12 in Eos. Bcl2L12 bound c-Myc, the transcription factor of Fas ligand (FasL), to prevent c-Myc from binding to the FasL promoter, to restrict the FasL gene transcription in Eos. Inhibition of Bcl2L12 prevented the induction of eosinophilia and Mcd-like inflammation in the mouse heart. Conclusions: The Bcl2L12 expression contributes to apoptosis defects in Eos of the Mcd heart. Blocking Bcl2L12 prevents the eosinophilia induction and alleviates Mcd-like inflammation in mice.

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Section: Resultsmentioning

confidence: 99%

RETRACTED: Inhibition of Bcl2L12 Attenuates Eosinophilia-Related Inflammation in the Heart

et al. 2020

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“…MiR-98 is one of the miRs interfering with the expression of the immune regulatory molecule IL-10 in B cells [ 14 ], and thus compromises the immune regulatory capacity in the body. For example, overexpression of miR-98 is associated with the B-cell-related immune inflammation [ 15 ]. Since deregulation of TSP1 is also found in compromising the B cells’ immune regulatory functions [ 1 , 16 ], we hypothesized that miR-98 is an important factor in the regulation of TSP1 expression in B cells in patients with asthma.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-98 interferes with thrombospondin 1 expression in peripheral B cells of patients with asthma

Chen

Chu

et al. 2017

Bioscience Reports

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Thrombospondin 1 (TSP1)-producing B cells are an important immune regulatory cell fraction in the body, which are compromised in a number of immune diseases. miRs are involved in the immune regulation. The present study aims to elucidate the mechanism by which miR-98 interferes with the expression of TSP1 in B cells of the peripheral blood system. In the present study, peripheral blood samples were collected from patients with allergic asthma. The B cells were isolated from the blood samples to be analyzed for the expression of miR-98 and TSP1. The results showed that the levels of miR-98 were higher, the levels of TSP1 were lower, in B cells isolated from the peripheral blood in patients with asthma. A negative correlation was identified between the data of miR-98 and TSP1 in B cells. Exposure to T helper (Th) 2 (Th2) cytokine, interleukin (IL)-13, increased the expression of miR-98 and suppressed the expression of TSP1 in peripheral B cells, which was abolished by knocking down the miR-98 gene. In conclusion, miR-98 can suppress the expression of TSP1 in the peripheral B cells of patients with allergic asthma.

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“…As noted by previous literature, miR-98 was downregulated in tumors, including non-small-cell lung cancer [20], leukemia [21], hepatocellular carcinoma [22], and breast cancer [23]. Chen et al reported that the expression of miR-98 was upregulated in B cells isolated from mouse hearts with myocarditis [24]. In our study, the expression of miR-98 was remarkably lower in SLE PBMCs compared to that in HC PBMCs.…”

Section: Discussionmentioning

confidence: 94%

miR-98 Modulates Cytokine Production from Human PBMCs in Systemic Lupus Erythematosus by Targeting IL-6 mRNA

Yuan

Tang

Chen

et al. 2019

Journal of Immunology Research

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Objective There is evidence that interleukin-6 (IL-6) upregulation plays a critical role in immunopathology of systemic lupus erythematosus (SLE). MicroRNA- (miRNA-) 98 was predicted to bind with the 3′-untranslated region (3′-UTR) of IL-6 gene. We hypothesized miR-98 through its regulation of IL-6 gene expression to influence cytokine production from peripheral blood mononuclear cells (PBMCs) in SLE. Methods The expression of miR-98 and IL-6 mRNA in the PBMCs of 41 SLE patients and 20 healthy controls (HC) was detected by quantitative reverse transcription PCR (qRT-PCR). The correlations between miR-98 expression and clinical features were evaluated. Luciferase reporter assay was performed to identify miR-98 targets. miR-98 mimics, miR-98 inhibitor, and IL-6 overexpression vector were generated. Cell viability of PBMCs was assessed using MTT assay. Gene expression and protein level were determined by qRT-PCR and Western blotting. TNF-α, IL-8, IL-1β, and IL-10 levels in cultured supernatants were quantified using ELISA. Results The expression of miR-98 was downregulated in PBMCs of SLE patients, and its expression is negatively associated with IL-6 levels. miR-98 expression was correlated with disease activity, lupus nephritis, and anti-dsDNA antibody. IL-6 mRNA was a target gene of miR-98. IL-6 overexpression promoted the proliferation of PBMCs and increased the levels of TNF-α, IL-8, IL-1β, and IL-10. Those effects were further enhanced by miR-98 inhibitor, while were suppressed by miR-98 mimics. miR-98 regulated the levels of STAT3 phosphorylation via its target gene IL-6. Conclusion The current study revealed that miR-98 could ameliorate STAT3-mediated cell proliferation and inflammatory cytokine production via its target gene IL-6 in patients with SLE. These results suggest that miR-98 might serve as a potential target for SLE treatment and other IL-6-mediated diseases.

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MicroRNA-98 plays a critical role in experimental myocarditis

Cited by 26 publications

References 24 publications

RETRACTED: Inhibition of Bcl2L12 Attenuates Eosinophilia-Related Inflammation in the Heart

RETRACTED: Inhibition of Bcl2L12 Attenuates Eosinophilia-Related Inflammation in the Heart

MicroRNA-98 interferes with thrombospondin 1 expression in peripheral B cells of patients with asthma

miR-98 Modulates Cytokine Production from Human PBMCs in Systemic Lupus Erythematosus by Targeting IL-6 mRNA

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