MiR-33 promotes myocardial fibrosis by inhibiting MMP16 and stimulating p38 MAPK signaling

Chen, Zhe; Ding, Hua‐Sheng; Guo, Xin; Shen, Jin; Fan, Di; Huang, Yan; Huang, Congxin

doi:10.18632/oncotarget.25173

Cited by 20 publications

(12 citation statements)

References 24 publications

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“…SPP1, a protein with proinflammatory and profibrotic properties, has already been demonstrated to take part in cardiac and lung fibrosis 59,60 . MMP16 protein activates MMP2 protein which in turn degrades type III collagen and was demonstrated to be decreased in the myocardial fibrosis 61 .…”

Section: Resultsmentioning

confidence: 99%

Circulating miRNA-181b-5p, miRNA-223-3p, miRNA-210-3p, let 7i-5p, miRNA-21-5p and miRNA-29a-3p in patients with localized scleroderma as potential biomarkers

Wolska-Gawron

Bartosińska

Rusek

et al. 2020

Sci Rep

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Localized scleroderma (LoSc) is a rare disease manifested by an inflammation and sclerosis of the skin. The latest studies focused on glycoprotein Krebs von den Lungen-6, surfactant protein-D, chemokine ligand 18 and dipeptidylpeptidase 4 as potential biomarkers of skin fibrosis in systemic scleroderma. Our study aimed to identify 6 miRNAs with elevated or decreased levels in 38 LoSc patients (31 females, 7 males) compared to healthy volunteers (HVs) and to correlate the selected miRNAs’ serum levels with the severity and the clinical symptoms of LoSc and some laboratory parameters with the selected miRNAs’ serum levels. The serum levels of miRNAs, i.e. miRNA-181b-5p, miRNA-223-3p, miRNA-21-5p, let 7i-5p, miRNA-29a-3p and miRNA-210-3p were significantly increased in the LoSc patients compared to the HVs. The level of let-7i increase in the female LoSc patients correlated negatively with BSA (r = − 0.355, p = 0.049) and mLoSSI (r = − 0.432, p = 0.015). Moreover, the female patients with inactive LoSc had significantly higher level of let-7i (2.68-fold on average) in comparison to those with active disease (p = 0.045). The exact role of those molecules has not been revealed in LoSc and a long-term longitudinal research is pivotal to confirm their prognostic value.

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Section: Resultsmentioning

confidence: 99%

Circulating miRNA-181b-5p, miRNA-223-3p, miRNA-210-3p, let 7i-5p, miRNA-21-5p and miRNA-29a-3p in patients with localized scleroderma as potential biomarkers

Wolska-Gawron

Bartosińska

Rusek

et al. 2020

Sci Rep

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“…Thus, it is possible that interaction with other RNA‐binding proteins and miRNAs may play a role in regulating the stability of ECM marker mRNAs or that HuR is controlling translation. Further support for these possibilities comes from a study in cardiac fibroblasts, where miR‐33a increases the expression of COL1A1 and COL3A1 (in vivo and in vitro) and that knockdown of miR‐33a is sufficient to decrease their expression (Chen et al, 2018). This effect of miR‐33a on COL1A1 and COL3A1 expression is mediated through the p38 MAPK pathway but not through the TGFβ1/SMAD pathway (Chen et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Human antigen R promotes lung fibroblast differentiation to myofibroblasts and increases extracellular matrix production

Al-Habeeb

Aloufi

Traboulsi

et al. 2021

Journal Cellular Physiology

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Idiopathic pulmonary fibrosis (IPF) is a disease of progressive scarring caused by excessive extracellular matrix (ECM) deposition and activation of α‐SMA‐expressing myofibroblasts. Human antigen R (HuR) is an RNA binding protein that promotes protein translation. Upon translocation from the nucleus to the cytoplasm, HuR functions to stabilize messenger RNA (mRNA) to increase protein levels. However, the role of HuR in promoting ECM production, myofibroblast differentiation, and lung fibrosis is unknown. Human lung fibroblasts (HLFs) treated with transforming growth factor β1 (TGF‐β1) showed a significant increase in translocation of HuR from the nucleus to the cytoplasm. TGF‐β‐treated HLFs that were transfected with HuR small interfering RNA had a significant reduction in α‐SMA protein as well as the ECM proteins COL1A1, COL3A, and FN1. HuR was also bound to mRNA for ACTA2, COL1A1, COL3A1, and FN. HuR knockdown affected the mRNA stability of ACTA2 but not that of the ECM genes COL1A1, COL3A1, or FN. In mouse models of pulmonary fibrosis, there was higher cytoplasmic HuR in lung structural cells compared to control mice. In human IPF lungs, there was also more cytoplasmic HuR. This study is the first to show that HuR in lung fibroblasts controls their differentiation to myofibroblasts and consequent ECM production. Further research on HuR could assist in establishing the basis for the development of new target therapy for fibrotic diseases, such as IPF.

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“…Four of these 6 miRNAs identified only in the I/R+CRP group (miR-33, miR-409-3p, miR-384-3p and miR-101a) were found to be involved in myocardial disease. Recent studies have shown that the expression level of miR-33 is elevated in heart failure [31] and that miR-33 promotes myocardial fibrosis [32] and vascular atherosclerosis [33]. Currently, miR-33 is being considered as a new therapeutic target [34].…”

Section: Discussionmentioning

confidence: 99%

High serum CRP influences myocardial miRNA profiles in ischemia-reperfusion injury of rat heart

Kim

et al. 2019

PLoS ONE

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Objective Prognosis of myocardial infarction tends to be worse when serum C-reactive protein (CRP) level is high. miRNAs are also known to be involved in different pathogeneses of heart diseases such as myocardial infarction. However, how CRP is involved in myocardial infarction has not been fully elucidated. We hypothesized that serum CRP changes the miRNA profile during ischemia-reperfusion injury (IRI) of the myocardium. To confirm this hypothesis, we performed global miRNA expression profiling of myocardium using IRI and CRP infusion rat model. Methods After ligation of the coronary artery of rat hearts, human serum CRP was intravenously injected, and reperfusion was performed (I/R+CRP group, n = 6). Control group consisted of the sham group (n = 3), IV CRP infusion group (CRP only, n = 3), and the I/R-only group (I/R only, n = 5). We evaluated 423 miRNA expression in non-ischemic areas and areas at risk (AAR) of each group using NanoString nCounter miRNA expression assay. Results MiR-124 was downregulated in non-ischemic myocardium in CRP-only group. In AAR, 7 miRNAs were commonly upregulated in both I/R-only and I/R+CRP groups. And additional 6 miRNAs were upregulated in the I/R+CRP group (miR-33, miR-409-3p, miR-384-3p, miR-3562, miR-101a, and miR-340-5p). Similarly, in the non-ischemic areas, 6 miRNAs were commonly upregulated in both I/R-only and I/R+CRP groups, and additional 5 miRNAs changed in the I/R+CRP group (upregulation of miR-3559-5p, miR-499, and miR-21 and downregulation of miR-500 and miR-532-3p). Conclusion We showed that when serum CRP level is high, IRI results in multiple miRNA profile changes not only in ischemic areas but also in non-ischemic myocardium. Our results may provide a strong basis for studying the role of CRP and miRNAs in ischemic heart disease.

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MiR-33 promotes myocardial fibrosis by inhibiting MMP16 and stimulating p38 MAPK signaling

Cited by 20 publications

References 24 publications

Circulating miRNA-181b-5p, miRNA-223-3p, miRNA-210-3p, let 7i-5p, miRNA-21-5p and miRNA-29a-3p in patients with localized scleroderma as potential biomarkers

Circulating miRNA-181b-5p, miRNA-223-3p, miRNA-210-3p, let 7i-5p, miRNA-21-5p and miRNA-29a-3p in patients with localized scleroderma as potential biomarkers

Human antigen R promotes lung fibroblast differentiation to myofibroblasts and increases extracellular matrix production

High serum CRP influences myocardial miRNA profiles in ischemia-reperfusion injury of rat heart

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