Therapeutic potential of targeting microRNAs to regulate cardiac fibrosis: miR-433 a new fibrotic player

Ooi, Jenny Y. Y.; Bernardo, Bianca C.; McMullen, Julie R.

doi:10.21037/atm.2016.12.01

Cited by 9 publications

(7 citation statements)

References 20 publications

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“…Downregulated AZIN1 induces TGF-β1 pathway, whereas decreased JNK1 results in ERK and p38 kinase activation, causing Smad3 activation and eventually leading to cardiac fibrosis ( 123 ). In another study in that same year, Ooi et al ( 161 ) suggested that AZIN1 expression reduction induces TGF-β/Smad3 signaling activation in CFs; (III) reduced JNK level would enhance ERK, P38 kinase, and Smad3 phosphorylation, and that is in turn associated with proliferation and differentiation of fibroblast into myofibroblasts.…”

Section: The Relationship Between Ncrnas and Tgf-β/smad Signaling In mentioning

confidence: 99%

Pivotal Role of TGF-β/Smad Signaling in Cardiac Fibrosis: Non-coding RNAs as Effectual Players

Saadat

Noureddini

Mahjoubin‐Tehran

et al. 2021

Front. Cardiovasc. Med.

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Unintended cardiac fibroblast proliferation in many pathophysiological heart conditions, known as cardiac fibrosis, results in pooling of extracellular matrix (ECM) proteins in the heart muscle. Transforming growth factor β (TGF-β) as a pivotal cytokine/growth factor stimulates fibroblasts and hastens ECM production in injured tissues. The TGF-β receptor is a heterodimeric receptor complex on the plasma membrane, made up from TGF-β type I, as well as type II receptors, giving rise to Smad2 and Smad3 transcription factors phosphorylation upon canonical signaling. Phosphorylated Smad2, Smad3, and cytoplasmic Smad4 intercommunicate to transfer the signal to the nucleus, culminating in provoked gene transcription. Additionally, TGF-β receptor complex activation starts up non-canonical signaling that lead to the mitogen-stimulated protein kinase cascade activation, inducing p38, JNK1/2 (c-Jun NH2-terminal kinase 1/2), and ERK1/2 (extracellular signal–regulated kinase 1/2) signaling. TGF-β not only activates fibroblasts and stimulates them to differentiate into myofibroblasts, which produce ECM proteins, but also promotes fibroblast proliferation. Non-coding RNAs (ncRNAs) are important regulators of numerous pathways along with cellular procedures. MicroRNAs and circular long ncRNAs, combined with long ncRNAs, are capable of affecting TGF-β/Smad signaling, leading to cardiac fibrosis. More comprehensive knowledge based on these processes may bring about new diagnostic and therapeutic approaches for different cardiac disorders.

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Section: The Relationship Between Ncrnas and Tgf-β/smad Signaling In mentioning

confidence: 99%

Pivotal Role of TGF-β/Smad Signaling in Cardiac Fibrosis: Non-coding RNAs as Effectual Players

Saadat

Noureddini

Mahjoubin‐Tehran

et al. 2021

Front. Cardiovasc. Med.

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“…It is necessary to note that with developing fibrosis, miRNAs are produced not only by cardiomyocytes but also by fibroblasts, leukocytes, and other cells of the myocardium. miR-433 plays a crucial role in regulating fibrosis ( Tao et al, 2016 ), with JNK1 and AZIN1 proposed as the target genes that mediate the fibrotic effect ( Ooi et al, 2016 ). It is important to note that MiR-223 is considered to be a marker of heart failure ( Zhang et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Cardiac miRNA expression during the development of chronic anthracycline-induced cardiomyopathy using an experimental rabbit model

Adamcova,

Parova,

Lencova-Popelova

et al. 2024

Front. Pharmacol.

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Background: Anthracycline cardiotoxicity is a well-known complication of cancer treatment, and miRNAs have emerged as a key driver in the pathogenesis of cardiovascular diseases. This study aimed to investigate the expression of miRNAs in the myocardium in early and late stages of chronic anthracycline induced cardiotoxicity to determine whether this expression is associated with the severity of cardiac damage.Method: Cardiotoxicity was induced in rabbits via daunorubicin administration (daunorubicin, 3 mg/kg/week; for five and 10 weeks), while the control group received saline solution. Myocardial miRNA expression was first screened using TaqMan Advanced miRNA microfluidic card assays, after which 32 miRNAs were selected for targeted analysis using qRT-PCR.Results: The first subclinical signs of cardiotoxicity (significant increase in plasma cardiac troponin T) were observed after 5 weeks of daunorubicin treatment. At this time point, 10 miRNAs (including members of the miRNA-34 and 21 families) showed significant upregulation relative to the control group, with the most intense change observed for miRNA-1298-5p (29-fold change, p < 0.01). After 10 weeks of daunorubicin treatment, when a further rise in cTnT was accompanied by significant left ventricle systolic dysfunction, only miR-504-5p was significantly (p < 0.01) downregulated, whereas 10 miRNAs were significantly upregulated relative to the control group; at this time-point, the most intense change was observed for miR-34a-5p (76-fold change). Strong correlations were found between the expression of multiple miRNAs (including miR-34 and mir-21 family and miR-1298-5p) and quantitative indices of toxic damage in both the early and late phases of cardiotoxicity development. Furthermore, plasma levels of miR-34a-5p were strongly correlated with the myocardial expression of this miRNA.Conclusion: To the best of our knowledge, this is the first study that describes alterations in miRNA expression in the myocardium during the transition from subclinical, ANT-induced cardiotoxicity to an overt cardiotoxic phenotype; we also revealed how these changes in miRNA expression are strongly correlated with quantitative markers of cardiotoxicity.

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“…It has been widely demonstrated that mRNAs could regulate diverse biological processes and mRNAs have been studied extensively in fibrosis of different organs [16,19,20]; however, only limited information about mRNAs in the development of HTFs fibrosis and scar formation. As showed in pathophysiological processes of pulmonary fibrosis, down-regulation of miR-26a was detected in the lungs of mice with experimental pulmonary fibrosis [21].…”

Section: Discussionmentioning

confidence: 99%

A key role of microRNA-26a in the scar formation after glaucoma filtration surgery

Wang

Deng

2017

Artificial Cells, Nanomedicine, and Biotechnology

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Glaucoma is one of the leading causes of blind worldwide. Post-operative scar formation of filtering tract was one of the main reasons for failure of glaucoma filtration surgery. In this study, we conducted several experiments to detect the expression of miR-26a in the scar tissue in filtering tract and then detect its potential biological effects as well as its target gene. In our present study, it was found that miR-26a was significantly down-regulated in filtering tract scar. Advanced study on the association between the miR-26a and connective tissue growth factor (CTGF) micro RNA (mRNA) showed that miR-26a was inversely correlated with CTGF mRNA level. Advanced biological studies showed that overexpression of miR-26a could decrease the cell viability and migration ability of human Tenon's fibroblasts (HTFs) fibrosis in vitro model. It was also found that miR-26a might up-regulate the apoptotic level of HTFs. Through protein expression detection and luciferase reporter assay, it was found that miR-26a could produce functions that directly target the CTGF. In conclusion, the key finding of the current study is that miR-26a can suppress the activation of HTFs by transforming growth factor (TGF)-β by targeting CTGF. This data indicates that miR-26a plays an essential role in the formation of filtering tract scar and function as a potential drug target.

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Therapeutic potential of targeting microRNAs to regulate cardiac fibrosis: miR-433 a new fibrotic player

Cited by 9 publications

References 20 publications

Pivotal Role of TGF-β/Smad Signaling in Cardiac Fibrosis: Non-coding RNAs as Effectual Players

Pivotal Role of TGF-β/Smad Signaling in Cardiac Fibrosis: Non-coding RNAs as Effectual Players

Cardiac miRNA expression during the development of chronic anthracycline-induced cardiomyopathy using an experimental rabbit model

A key role of microRNA-26a in the scar formation after glaucoma filtration surgery

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