DNMT3A controls miR-200b in cardiac fibroblast autophagy and cardiac fibrosis

Zhao, Xudong; Qin, Run-He; Yang, Jingjing; Xu, Shijie; Tao, Hui; Ding, Xiaowen; Shi, Kai-Hu

doi:10.1007/s00011-018-1159-2

Cited by 37 publications

(23 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…At the same time, the expressions of cardiac hypertrophy marker proteins BNP and β-MHC, as well as intracellular calcium signal, were also significantly inhibited. Recently, accumulate evidence indicates that autophagy is activated in aortic banding model 35,36. Intriguingly, our results…”

supporting

confidence: 79%

MiR‐103 inhibiting cardiac hypertrophy through inactivation of myocardial cell autophagy via targeting TRPV3 channel in rat hearts

Ren

Mingyao

et al. 2019

J Cellular Molecular Medi

View full text Add to dashboard Cite

Cardiac hypertrophy is a common pathological change frequently accompanied by chronic hypertension and myocardial infarction. Nevertheless, the pathophysiological mechanisms of cardiac hypertrophy have never been elucidated. Recent studies indicated that miR‐103 expression was significantly decreased in heart failure patients. However, less is known about the role of miR‐103 in cardiac hypertrophy. The present study was designed to investigate the relationship between miR‐103 and the mechanism of pressure overload‐induced cardiac hypertrophy. TRPV 3 protein, cardiac hypertrophy marker proteins ( BNP and β‐ MHC ) and autophagy associated proteins (Beclin‐1 and LC 3‐ II ) were up‐regulated, as well as, miR‐103 expression and autophagy associated proteins (p62) were down‐regulated in cardiac hypertrophy models in vivo and in vitro respectively. Further results indicated that silencing TRPV 3 or forcing overexpression of miR‐103 could dramatically inhibit cell surface area, relative fluorescence intensity of Ca 2+ signal and the expressions of BNP , β‐ MHC , Beclin‐1 and LC 3‐ II , but promote p62 expression. Moreover, TRPV 3 protein was decreased in neonatal rat ventricular myocyte transfected with miR‐103, but increased by AMO ‐103. Co‐transfection of the miR‐103 with the luciferase reporter vector into HEK 293 cells caused a sharp decrease in luciferase activity compared with transfection of the luciferase vector alone. The miR‐103‐induced depression of luciferase activity was rescued by an AMO ‐103. These findings suggested that TRPV 3 was a direct target of miR‐103. In conclusion, miR‐103 could attenuate cardiomyocyte hypertrophy partly by reducing cardiac autophagy activity through the targeted inhibition of TRPV 3 signalling in the pressure‐overloaded rat hearts.

show abstract

supporting

confidence: 79%

MiR‐103 inhibiting cardiac hypertrophy through inactivation of myocardial cell autophagy via targeting TRPV3 channel in rat hearts

Ren

Mingyao

et al. 2019

J Cellular Molecular Medi

View full text Add to dashboard Cite

show abstract

“…Recent studies have shown that miR-200b plays a role in the development of fibrosis in a variety of tissues, including cardiac fibroblast fibrosis, precancerous oral submucous fibrosis, early pulmonary fibrosis, interstitial fibrosis, and liver fibrosis [ 9 , 29 , 44 , 46 ]. Moreover, it has been documented that miR-222 promotes the progression of liver fibrosis through regulating the activation of HSCs [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

Circulating miRNAs as footprints for liver fibrosis grading in schistosomiasis

Cai

Olveda

et al. 2018

EBioMedicine

View full text Add to dashboard Cite

BackgroundChronic infection with Schistosoma japonicum or S. mansoni results in hepatic fibrosis of the human host. Staging fibrosis is crucial for the prognosis and to determine the rapid need of treatment in patients with schistosomiasis.MethodsTo establish whether there is a correlation between circulating microRNA (miRNA) level and fibrosis progression in schistosomiasis, ten miRNAs were selected to assess their potential in grading schistosomiasis liver fibrosis. This was done firstly in two mouse strains (C57BL/6 and BALB/c) to determine the temporal expression profiles in serum over the course of S. japonicum infection, and then within a cohort of 163 schistosomiasis japonica patients with different grades of liver fibrosis.FindingFour miRNAs (miR-150-5p, let-7a-5p, let-7d-5p and miR-146a-5p) were able to distinguish patients with mild versus severe fibrosis. The level of serum miR-150-5p showed the most promising potential for grading hepatic fibrosis in schistosomiasis. The diagnostic performance of miR-150-5p in discriminating mild from severe fibrosis is comparable with that of the ELF test and serum HA level. In addition, the serum levels of the four miRNAs rebounded in infected C57BL/6 mice, after 6 months post treatment, following the regression of liver fibrosis, thereby providing further support for the utility of these miRNAs in grading schistosomal hepatic fibrosis.Interpretation.Circulating miRNAs can be a supplementary tool for assessing hepatic fibrosis in human schistosomiasis.Fund (NHMRC) of Australia (APP1102926, APP1037304 and APP1098244).

show abstract

“…For example, the expression of miRNAs is frequently regulated by methylation of the corresponding DNA locus. The transcription of miR-200 family members requires, in fact, DNA demethylation at the promoter level and is enhanced by reducing the activity of DNMTs [64]. In a rat model of cardiac fibrosis and abdominal aortic constriction [64], miR-200b inhibited the expression of LC3BII/I, which is a trigger signal in cardiac myofibroblast conversion, a process that increases autophagy.…”

Section: Non-coding Rna and Their Promoter Methylation In Cardiovascumentioning

confidence: 99%

“…The transcription of miR-200 family members requires, in fact, DNA demethylation at the promoter level and is enhanced by reducing the activity of DNMTs [64]. In a rat model of cardiac fibrosis and abdominal aortic constriction [64], miR-200b inhibited the expression of LC3BII/I, which is a trigger signal in cardiac myofibroblast conversion, a process that increases autophagy. HHcy is a known risk factor for ischemic stroke [65], in which methylation occurs on non-coding RNA promoters [66] and specific mRNAs, as previously described [49].…”

Section: Non-coding Rna and Their Promoter Methylation In Cardiovascumentioning

confidence: 99%

Epigenetic Signaling and RNA Regulation in Cardiovascular Diseases

Mongelli

Atlante

Bachetti

et al. 2020

IJMS

View full text Add to dashboard Cite

RNA epigenetics is perhaps the most recent field of interest for translational epigeneticists. RNA modifications create such an extensive network of epigenetically driven combinations whose role in physiology and pathophysiology is still far from being elucidated. Not surprisingly, some of the players determining changes in RNA structure are in common with those involved in DNA and chromatin structure regulation, while other molecules seem very specific to RNA. It is envisaged, then, that new small molecules, acting selectively on RNA epigenetic changes, will be reported soon, opening new therapeutic interventions based on the correction of the RNA epigenetic landscape. In this review, we shall summarize some aspects of RNA epigenetics limited to those in which the potential clinical translatability to cardiovascular disease is emerging.

show abstract

DNMT3A controls miR-200b in cardiac fibroblast autophagy and cardiac fibrosis

Abstract: Taken together, these findings indicate that DNMT3A regulation of miR-200b controls cardiac fibroblast autophagy during cardiac fibrosis and provide a basis for the development of therapies for cardiac fibrosis.

Cited by 37 publications

References 19 publications

MiR‐103 inhibiting cardiac hypertrophy through inactivation of myocardial cell autophagy via targeting TRPV3 channel in rat hearts

MiR‐103 inhibiting cardiac hypertrophy through inactivation of myocardial cell autophagy via targeting TRPV3 channel in rat hearts

Circulating miRNAs as footprints for liver fibrosis grading in schistosomiasis

Epigenetic Signaling and RNA Regulation in Cardiovascular Diseases

Contact Info

Product

Resources

About