Comprehensive microRNA profiling reveals potential augmentation of the IL1 pathway in rheumatic heart valve disease

Lu, Qiyu; Sun, Yihong; Duan, Yuyin; Li, Bin; Xia, Jianming; Yu, Shengwen; Zhang, Guimin

doi:10.1186/s12872-018-0788-2

Cited by 20 publications

(25 citation statements)

References 21 publications

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“…These molecules can serve as molecular biological markers for the early diagnosis of various clinical diseases. It was reported that some miRNAs are specifically expressed in heart tissue and pulmonary hypertension [ 15 , 16 ]. Nevertheless, no specific expression of miRNAs such as miR-208 have been found in other tissues.…”

Section: Discussionmentioning

confidence: 99%

miRNA-1183-targeted regulation of Bcl-2 contributes to the pathogenesis of rheumatic heart disease

Zhu

Zhou

et al. 2020

Bioscience Reports

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To determine whether up-regulation of miR-1183 targeting the gene for anti-apoptotic factor, B cell lymphoma-2 (BCL-2) contributes to apoptosis in patients with rheumatic heart disease (RHD). Peripheral blood samples were isolated for miR-1183 characterization. The function of miRNA-1183 in RHD using miRNA mimic on PBMCs and THP-1 cell models. The binding of miR-1183 and Bcl-2 gene was confirmed by luciferase activity test.We also measured expression levels of BCL-2 in heart valve tissue from patients with RHD using ELISA and immunohistochemistry. In silico analysis and reporter gene assays indicated that miR-1183 directly targets the mRNA encoding BCL-2. It is found that miR-1183 binds directly to the 3’ UTR of the BCL-2 mRNA and downregulates the mRNA and protein levels of BCL-2.Overexpression of miR-1183 in RHD patients and cell lines downregulated BCL-2 expression and induced apoptosis. With the progression of the disease, the expression of BCL-2 in the heart valve tissue of patients with RHD decreased. MiRNA-1183 is upregulated in RHD and induces cardiac myocyte apoptosis through direct targeting and suppression of BCL-2, both of which might play important roles in RHD pathogenesis. During the compensatory period of RHD, up-regulated miR-1183 destroyed the balance of apoptosis proteins (Bax、BAK) in bcl-2 family, enhance the apoptosis cascade reaction and reduce the anti apoptosis effect.The significantly higher expression levels of miR-1183 appear to play distinct roles in RHD pathogenesis by regulation BCL-2, possibly affecting myocardial apoptosis and remodeling in the context of RHD.

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Section: Discussionmentioning

confidence: 99%

miRNA-1183-targeted regulation of Bcl-2 contributes to the pathogenesis of rheumatic heart disease

Zhu

Zhou

et al. 2020

Bioscience Reports

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“…Several studies have reported that the expression of miRNAs is altered in patients with chronic RHd, including miR-205-3p, miR-1183 and miR-101. These miRNAs regulate the progression of RHd by targeting different pathways, such as IL-1β and TLR2 (17)(18)(19). The mechanism of action of miR-155-5p in RHd is still unclear, but scholars have reported that miR-155 is involved in autoimmunity, inflammation and fibrosis (20)(21)(22).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of miR‑155‑5p attenuates the valvular damage induced by rheumatic heart disease

Chen

Wen

et al. 2019

Int J Mol Med

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Autoimmunity is involved in the valvular damage caused by rheumatic heart disease (RHd). Increased evidence has linked microRNAs (miRNAs/miRs) to autoimmune disease. Signal transducer and activator of transcription 3 (STAT3) and sphingosine-1-phosphate receptor 1 (S1PR1) and suppressor of cytokine signaling 1 (SOcS1) have been widely studied for their roles in autoimmunity and inflammation. Thus, the current study aims to investigate the role played by miR-155-5p in RHd-induced valvular damage via the S1PR1, SOcS1/STAT3 and interleukin (IL)-6/STAT3 signaling pathways. An RHd rat model was induced by inactivated Group A streptococci and complete Freund's adjuvant. A recombinant adeno-associated virus (AAV-miR155-inhibitor) was used to inhibit the expression of miR-155-5p in the heart. Inflammation and fibrosis were assessed by hematoxylin and eosin staining and Sirius red staining. The expression of miR-155-5p in valvular tissues and serum exosomes was detected by reverse transcription-quantitative PcR. S1PR1, SOcS1, STAT3, phosphorylated STAT3, IL-6 and IL-17 protein expression was detected by western blotting and immunohistochemistry. The relationships between miR-155-5p and S1PR1 and SOcS1 were detected by dual luciferase assays. cytokine concentrations were measured by ELISA. The expression of miR-155-5p in valve tissues and serum exosomes was increased along with decreased S1PR1 and activated SOcS1/STAT3 signaling in the RHd model. The expression of IL-6 and IL-17 was increased in the valves and the serum. dual luciferase assays showed that miR-155-5p directly targeted S1PR1 and SOcS1. Inhibition of valvular miR-155-5p through AAV pretreatment increased S1PR1 expression and inhibited activation of the SOcS1/STAT3 signal pathway as a result of attenuated valvular inflammation and fibrosis as well as a decrease in IL-6 and IL-17 in the valves and serum. These results suggest that inhibition of miR-155-5p can reduce RHd-induced valvular damage via the S1PR1, SOcS1/STAT3 and IL-6/STAT3 signaling pathways.

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“…Our hub genes and cross-linked miRNAs results in Table 2 also demonstrated that miRNA-199b-5p may directly target ACTN2 and ANK2 genes which are both suppressed in CAVS, suggesting the effects of these molecules on the pathogenesis of aortic stenosis. In addition, miRNA-374b [49], miRNA-340 [50] and miRNA-203 [51] have also been reported to be abnormally expressed in aortic stenosis patients, which can be used as a diagnostic/ prognostic biomarker of CAVS in the future. However, during the process of the disease, genetic alteration may occur secondary to some pathological changes.…”

Section: Discussionmentioning

confidence: 99%

miRNA-mRNA crosstalk in myocardial ischemia induced by calcified aortic valve stenosis

Duan

Cao

Tang

et al. 2019

Aging

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Aortic valve stenosis is the most common cause of morbidity and mortality in valvular heart disease in aged people. Both microRNA (miRNA) and mRNA are potential targets for the diagnosis and therapeutic intervention of myocardial ischemia induced by calcified aortic valve stenosis (CAVS), with unclear mechanisms. Here, 3 gene expression profiles of 47 male participants were applied to generate shared differentially expressed genes (DEGs) with significant major biological functions. Moreover, 20 hub genes were generated by a Weighted Genes Co-Expression Network Analysis (WGCNA) and were cross-linked to miRNA based on miRanda/miRwalk2 databases. Integrated miRNA/mRNA analysis identified several novel miRNAs and targeted genes as diagnostic/prognostic biomarkers or therapeutic targets in CAVS patients. In addition, the clinical data suggested that myocardial hypertrophy and myocardial ischemia in CAVS patients are likely associated with hub genes and the upstream regulatory miRNAs. Together, our data provide evidence that miRNAs and their targeted genes play an important role in the pathogenesis of myocardial hypertrophy and ischemia in patients with CAVS.

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Comprehensive microRNA profiling reveals potential augmentation of the IL1 pathway in rheumatic heart valve disease

Cited by 20 publications

References 21 publications

miRNA-1183-targeted regulation of Bcl-2 contributes to the pathogenesis of rheumatic heart disease

miRNA-1183-targeted regulation of Bcl-2 contributes to the pathogenesis of rheumatic heart disease

Inhibition of miR‑155‑5p attenuates the valvular damage induced by rheumatic heart disease

miRNA-mRNA crosstalk in myocardial ischemia induced by calcified aortic valve stenosis

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