Anti-fibrotic Role of miR-214 in Thioacetamide-induced Liver Cirrhosis in Rats

Izawa, Takeshi; Horiuchi, Takashi; Atarashi, Machi; Kuwamura, Mitsuru; Yamate, Jyoji

doi:10.1177/0192623315573587

Cited by 18 publications

(20 citation statements)

References 25 publications

(42 reference statements)

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“…Therefore, our data have demonstrated the anti-fibrotic effect of miR-214-3p, instead of a pro-fibrotic effect, in cardiac fibrosis. This conclusion has been supported by previous studies showing the protective effect of miR-214 by inhibition of fibrosis [16, 19, 27]. …”

Section: Discussionsupporting

confidence: 82%

Targeting EZH1 and EZH2 contributes to the suppression of fibrosis-associated genes by miR-214-3p in cardiac myofibroblasts

et al. 2016

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The role of microRNA-214-3p (miR-214-3p) in cardiac fibrosis was not well illustrated. The present study aimed to investigate the expression and potential target of miR-214-3p in angiotensin II (Ang-II)-induced cardiac fibrosis. MiR-214-3p was markedly decreased in the fibrotic myocardium of a mouse Ang-II infusion model, but was upregulated in Ang-II-treated mouse myofibroblasts. Cardiac fibrosis was shown attenuated in Ang-II-infused mice received tail vein injection of miR-214-3p agomir. Consistently, miR-214-3p inhibited the expression of Col1a1 and Col3a1 in mouse myofibroblasts in vitro. MiR-214-3p could bind the 3′-UTRs of enhancer of zeste homolog 1 (EZH1) and −2, and suppressed EZH1 and −2 expressions at the transcriptional level. Functionally, miR-214-3p mimic, in parallel to EZH1 siRNA and EZH2 siRNA, could enhance peroxisome proliferator-activated receptor-γ (PPAR-γ) expression and inhibited the expression of Col1a1 and Col3a1 in myofibroblasts. In addition, enforced expression of EZH1 and −2, and knockdown of PPAR-γ resulted in the increase of Col1a1 and Col3a1 in myofibroblasts. Moreover, the NF-κB signal pathway was verified to mediate Ang-II-induced miR-214-3p expression in myofibroblasts. Taken together, our results revealed that EZH1 and −2 were novel targets of miR-214-3p, and miR-214-3p might be one potential miRNA for the prevention of cardiac fibrosis.

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Section: Discussionsupporting

confidence: 82%

Targeting EZH1 and EZH2 contributes to the suppression of fibrosis-associated genes by miR-214-3p in cardiac myofibroblasts

et al. 2016

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“…miRNA-214 can also inhibit bladder cancer growth by targeting PDRG1 gene (42). Moreover, Wan et al (43) report that miR-214 has a protective role in the post treatment for myocardial ischemia, and Izawa et al (44) discover that miR-214 effectively alleviates thioacetamide-induced cirrhosis and may have an anti-fibrotic effect. In the present study, we find that expression of miR-214 is reduced in both mononuclear cells from IM-resistant CML patients and K562R cells.…”

Section: Discussionmentioning

confidence: 99%

Decreased expression of microRNA‑214 contributes to imatinib mesylate resistance of chronic myeloid leukemia patients by upregulating ABCB1 gene expression

Jin¹,

Yao²,

Fang³

et al. 2018

Exp Ther Med

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The aim of the present study was to determine the expression of adenosine triphosphate binding cassette subfamily B member 1 (ABCB1) gene and its protein P-glycoprotein (PGP) in bone marrow mononuclear cells from chronic myeloid leukemia (CML) patients with imatinib mesylate (IM) resistance, or IM-resistant CML K562 cells. In addition, the molecular mechanism of action of microRNA (miR)-214 on ABCB1 in IM resistance was investigated. A total of 26 CML patients with IM resistance were included in the present study. In addition, 31 CML patients who did not have IM resistance were included as the control group. Bone marrow was collected from all subjects. The K562R cell line, which is a K562 cell line with IM resistance, was used for cellular studies. Reverse transcription-quantitative polymerase chain reaction was used to determine the expression of ABCB1 mRNA and miR-214 in cells. Western blotting was employed to determine the expression of PGP. Dual luciferase reporter assay was carried out to identify interactions between ABCB1 mRNA and miR-214. MTT assay was used to determine the survival rate of cells. ABCB1 mRNA and PGP expression was upregulated in bone marrow mononuclear cells from CML patients with IM resistance. K562R cells had higher ABCB1 and PGP expression than K562 cells, potentially due to their different sensitivity to IM. Expression miR-214 was decreased in bone marrow mononuclear cells from patients with IM resistance and K562R cells. Notably, miR-214 was able to bind with the 3′-untranslated region, seed region of ABCB1 mRNA to regulate its expression. In addition, elevated expression of miR-214 restored IM sensitivity to K562R cells potentially by affecting ABCB1 expression. The present study demonstrated that upregulated expression of ABCB1 mRNA and PGP in bone marrow mononuclear cells from CML patients with IM resistance may be associated with the downregulation of miR-214. In addition, miR-214 may participate in the IM resistance of CML patients by regulating ABCB1 expression.

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“…miR‐21 has been comprehensively described in fibrosis because of its target relevance and important role in the modulation of the TGF‐β1 signalling pathway, related to the pathogenesis and progression of fibrosis in various organs . The association between miR‐21 and pulmonary, renal and cardiac fibrosis has been confirmed ; however, it is unclear whether miR‐21 plays a part in EndMT and perivascular fibrosis in the heart in T1DM. The purpose of this research is to evaluate the role and the mode of miR‐21 in regulating EndMT and cardiac perivascular fibrosis and to observe the influence of miR‐21 inhibition on the heart of diabetic cardiomyopathy.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of miR‐21 alleviated cardiac perivascular fibrosis via repressing EndMT in T1DM

Yao

Shi

et al. 2019

J Cellular Molecular Medi

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In type 1 and type 2 diabetes mellitus, increased cardiac fibrosis, stiffness and associated diastolic dysfunction may be the earliest pathological phenomena in diabetic cardiomyopathy. Endothelial‐mesenchymal transition (EndMT) in endothelia cells (ECs) is a critical cellular phenomenon that increases cardiac fibroblasts (CFs) and cardiac fibrosis in diabetic hearts. The purpose of this paper is to explore the molecular mechanism of miR‐21 regulating EndMT and cardiac perivascular fibrosis in diabetic cardiomyopathy. In vivo, hyperglycaemia up‐regulated the mRNA level of miR‐21, aggravated cardiac dysfunction and collagen deposition. The condition was recovered by inhibition of miR‐21 following with improving cardiac function and decreasing collagen deposition. miR‐21 inhibition decreased cardiac perivascular fibrosis by suppressing EndMT and up‐regulating SMAD7 whereas activating p‐SMAD2 and p‐SMAD3. In vitro, high glucose (HG) up‐regulated miR‐21 and induced EndMT in ECs, which was decreased by inhibition of miR‐21. A highly conserved binding site of NF‐κB located in miR‐21 5′‐UTR was identified. In ECs, SMAD7 is directly regulated by miR‐21. In conclusion, the pathway of NF‐κB/miR‐21/SMAD7 regulated the process of EndMT in T1DM, in diabetic cardiomyopathy, which may be regarded as a potential clinical therapeutic target for cardiac perivascular fibrosis.

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Anti-fibrotic Role of miR-214 in Thioacetamide-induced Liver Cirrhosis in Rats

Cited by 18 publications

References 25 publications

Targeting EZH1 and EZH2 contributes to the suppression of fibrosis-associated genes by miR-214-3p in cardiac myofibroblasts

Targeting EZH1 and EZH2 contributes to the suppression of fibrosis-associated genes by miR-214-3p in cardiac myofibroblasts

Decreased expression of microRNA‑214 contributes to imatinib mesylate resistance of chronic myeloid leukemia patients by upregulating ABCB1 gene expression

Inhibition of miR‐21 alleviated cardiac perivascular fibrosis via repressing EndMT in T1DM

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