MicroRNA-26a protects against cardiac hypertrophy via inhibiting GATA4 in rat model and cultured cardiomyocytes

Liu, Yan; Wang, Zhiqian; Xiao, Wenliang

doi:10.3892/mmr.2016.5574

Cited by 25 publications

(18 citation statements)

References 30 publications

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“…Over expression of miR-26b was found to suppress GATA-4 expression by targeting the 3'-UTR, leading to increased cardiomyocyte apoptosis (51). miR-26a attenuated cardiac hypertrophy via the targeting of GATA-4 in cultured cardiomyocytes (52). Downregulation of miR-208a suppressed doxorubicin-induced cardiomyocyte apoptosis by promoting GATA-4 (53).…”

Section: Discussionmentioning

confidence: 98%

Downregulation of miR-200c protects cardiomyocytes from hypoxia-induced apoptosis by targeting GATA-4

Chen

Zhang

Guo

et al. 2017

International Journal of Molecular Medicine

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Hypoxia-induced cardiomyocyte apoptosis plays an important role in the development of ischemic heart disease. MicroRNAs (miRNAs or miRs) are emerging as critical regulators of hypoxia-induced cardiomyocyte apoptosis. miR-200c is an miRNA that has been reported to be related to apoptosis in various pathological processes; however, its role in hypoxia‑induced cardiomyocyte apoptosis remains unclear. In the present study, we aimed to investigate the potential role and underlying mechanism of miR-200c in regulating hypoxia‑induced cardiomyocyte apoptosis. We found that miR-200c was significantly upregulated by hypoxia in cardiomyocytes, as detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The lactate dehydrogenase, MTT, Annexin V/propidium iodide apoptosis and caspase-3 activity assays showed that downregulation of miR-200c markedly improved cell survival and suppressed the apoptosis of cardiomyocytes in response to hypoxia. Bioinformatics analysis and the dual-luciferase reporter assay demonstrated that miR-200c directly targeted the 3'-untranslated region of GATA-4, an important transcription factor for cardiomyocyte survival. RT-qPCR and western blot analysis showed that suppression of miR-200c significantly increased GATA-4 expression. Furthermore, downregulation of miR-200c upregulated the expression of the anti-apoptotic gene Bcl-2. However, the protective effects against hypoxia induced by the downregulation of miR‑200c were significantly abolished by GATA-4 knockdown. Taken together, our results suggest that downregulation of miR-200c protects cardiomyocytes from hypoxia-induced apoptosis by targeting GATA-4, providing a potential therapeutic molecular target for the treatment of ischemic heart disease.

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Section: Discussionmentioning

confidence: 98%

Downregulation of miR-200c protects cardiomyocytes from hypoxia-induced apoptosis by targeting GATA-4

Chen

Zhang

Guo

et al. 2017

International Journal of Molecular Medicine

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“…Cardiac hypertrophy could be provoked by mechanical, neurohumoral stimuli and genetic mutation. We examined GATA4 signaling, which plays an important role in cardiomyocyte survival, vasoactive peptide-induced hypertrophic changes and maintenance of cardiac function in the adult heart [32,33], and found that expression of GATA4 in MAP4 KI mice was comparable to WT littermates at different ages (Fig. S10).…”

Section: Discussionmentioning

confidence: 99%

Microtubule associated protein 4 phosphorylation leads to pathological cardiac remodeling in mice

Zhang

et al. 2018

EBioMedicine

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BackgroundCardiac remodeling is a pathophysiological process that involves various changes in heart, including cardiac hypertrophy and fibrosis. Cardiac remodeling following pathological stimuli is common trigger leading to cardiac maladaptation and onset of heart failure, and their pathogenesis remains unclear.MethodsHeart specimens of tetralogy of Fallot (TOF) patients, myocardial infarction (MI) and transverse aortic constriction (TAC) mouse models were collected to determine changes of microtubule associated protein 4 (MAP4) phosphorylation. MAP4 (S667A, S737E and S760E) knock in (MAP4 KI) mouse and cultured neonatal mouse cardiomyocytes or fibroblasts were used to investigate changes of cardiac phenotypes and possible mechanisms with a variety of approaches, including functional, histocytological and pathological observations.FindingsElevated cardiac phosphorylation of MAP4 (S737 and S760) was observed in TOF patients, MI and TAC mouse models. In MAP4 KI mice, age-dependent cardiac phenotypes, including cardiac hypertrophy, fibrosis, diastolic and systolic dysfunction were observed. In addition, increased cardiomyocyte apoptosis together with microtubule disassembly and mitochondrial translocation of phosphorylated MAP4 was detected prior to the onset of cardiac remodeling, and p38/MAPK was demonstrated to be the possible signaling pathway that mediated MAP4 (S737 and S760) phosphorylation.InterpretationOur data reveal for the first time that MAP4 drives pathological cardiac remodeling through its phosphorylation. These findings bear the therapeutic potential to ameliorate pathological cardiac remodeling by attenuating MAP4 phosphorylation.FundThis work was supported by the Key Program of National Natural Science Foundation of China (No.81430042) and National Natural Science Foundation of China (No.81671913).

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“…MiR-26a plays a crucial role in the regulation of cardiomyocytes (Liu et al, 2016). Huang et al found that the up-regulation of miR-26a promoted the apoptosis of hypoxia-treated H9c2 cells, while emodin (15 and 20 mM) could negatively regulate the expression of miR-26a and reduce the apoptosis by regulating miR-26a (Huang et al, 2019).…”

Section: Mir-26amentioning

confidence: 99%

Molecular Mechanisms of Action of Emodin: As an Anti-Cardiovascular Disease Drug

Gao

Pang

et al. 2020

Front. Pharmacol.

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Emodin is a natural occurring anthraquinone derivative isolated from roots and barks of numerous plants, molds, and lichens. It is found to be an active ingredient in different Chinese herbs including Rheum palmatum and Polygonam multiflorum, and it is a pleiotropic molecule with diuretic, vasorelaxant, anti-bacterial, anti-viral, antiulcerogenic, anti-inflammatory, and anti-cancer effects. Moreover, emodin has also been shown to have a wide activity of anti-cardiovascular diseases. It is mainly involved in multiple molecular targets such as inflammatory, anti-apoptosis, anti-hypertrophy, antifibrosis, anti-oxidative damage, abnormal, and excessive proliferation of smooth muscle cells in cardiovascular diseases. As a new type of cardiovascular disease treatment drug, emodin has broad application prospects. However, a large amount of evidences detailing the effect of emodin on many signaling pathways and cellular functions in cardiovascular disease, the overall understanding of its mechanisms of action remains elusive. In addition, by describing the evidence of the effects of emodin in detail, the toxicity and poor oral bioavailability of mice have been continuously discovered. This review aims to describe a timely overview of emodin related to the treatment of cardiovascular disease. The emphasis is to summarize the pharmacological effects of emodin as an anticardiovascular drug, as well as the targets and its potential mechanisms. Furthermore, the treatment of emodin compared with conventional cardiovascular drugs or target inhibitors, the toxicity, pharmacokinetics and derivatives of emodin were discussed.

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MicroRNA-26a protects against cardiac hypertrophy via inhibiting GATA4 in rat model and cultured cardiomyocytes

Cited by 25 publications

References 30 publications

Downregulation of miR-200c protects cardiomyocytes from hypoxia-induced apoptosis by targeting GATA-4

Downregulation of miR-200c protects cardiomyocytes from hypoxia-induced apoptosis by targeting GATA-4

Microtubule associated protein 4 phosphorylation leads to pathological cardiac remodeling in mice

Molecular Mechanisms of Action of Emodin: As an Anti-Cardiovascular Disease Drug

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