YTHDF2 alleviates cardiac hypertrophy via regulating Myh7 mRNA decoy

Cell & Bioscience, Год журнала: 2021, Номер 11(1)

Опубликована: Июль 15, 2021

Abstract Background Pathological cardiac hypertrophy is a major contributor of heart failure (HF), which seriously threatens human’s health world widely. Deregulation m6A RNA methylation, and methyltransferases de-methyltransferases have been demonstrated to act essential roles in HF. Here, we studied the potential its underlying mechanisms Reader YTHDF proteins In this study, constructed HF mouse model by transverse aortic constriction surgery. Primary cardiomyocytes were isolated stimulated with isoproterenol (ISO) or phenylephrine (PHE) induce myocardial hypertrophy. Results Through single-cell RNA-seq analysis, immunofluorescent staining, HE Western blotting, real time-PCR detections, found that YTHDF2 mRNA protein level, but not YTHDF1 YTHDF3, was significantly increased during development. overexpression could efficiently alleviate Furthermore, through immunoprecipitation accompanied mass spectrometry Gene Ontology (GO) Kyoto Encyclopedia Genes Genomes (KEGG) pathway ISO stimulation did evidently affect YTHDF2-interacting proteins. However, PHE interacting Myh7 (beta-myosin heavy chain) mRNA, an important marker, m6A-dependent manner. Knockdown deletion YTH domain reversed protective effects on Finally, promoted expression enhancing Ythdf2 stability manner cardiomyocytes. Conclusions Overall, our results indicate suppresses via decoy This study highlights functional importance YTHDF2-dependent regulation hypertrophy, provides novel mechanistic insight into therapeutic YTHDF2.

Язык: Английский

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Histone acetyltransferase Kat2a regulates ferroptosis via enhancing Tfrc and Hmox1 expression in diabetic cardiomyopathy

Cell Death and Disease, Год журнала: 2024, Номер 15(6)

Опубликована: Июнь 10, 2024

Diabetic cardiomyopathy (DCM) is a prevalent myocardial microvascular complication of the myocardium with complex pathogenesis. Investigating pathogenesis DCM can significantly contribute to enhancing its prevention and treatment strategies. Our study revealed an upregulation lysine acetyltransferase 2 A (Kat2a) expression in DCM, accompanied by decrease N6-methyladenosine (m6A) modified Kat2a mRNA levels. Functionally, inhibition effectively ameliorated high glucose-induced cardiomyocyte injury both vitro vivo suppressing ferroptosis. Mechanistically, Demethylase alkB homolog 5 (Alkbh5) was found reduce m6A methylation levels on mRNA, leading upregulation. YTH domain family (Ythdf2) played crucial role as reader protein mediating degradation mRNA. Furthermore, promoted ferroptosis increasing Tfrc Hmox1 via enrichment H3K27ac H3K9ac their promoter regions. In conclusion, our findings unveil novel for Kat2a-ferroptosis axis pathogenesis, providing valuable insights potential clinical interventions.

Язык: Английский

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Studies on the fat mass and obesity-associated (FTO) gene and its impact on obesity-associated diseases

Genes & Diseases, Год журнала: 2022, Номер 10(6), С. 2351 - 2365

Опубликована: Май 6, 2022

Obesity has become a major health crisis in the past ∼50 years. The fat mass and obesity-associated (FTO) gene, identified by genome-wide association studies (GWAS), was first reported to be positively associated with obesity humans. Mice more copies of FTO gene were observed obese, while loss mice found protect from obesity. Later, encode an m6A RNA demethylase profound effect on many biological metabolic processes. In this review, we summarize recent that demonstrate critical roles regulatory mechanisms disease. Second, discuss ongoing debates concerning between polymorphisms Third, since several small molecule drugs micronutrients have been regulate homeostasis through controlling expression or activity FTO, highlight broad potential targeting for treatment. Improving our understanding underlying may provide new approaches treating diseases.

Язык: Английский

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Novel Therapies for the Treatment of Cardiac Fibrosis Following Myocardial Infarction

Biomedicines, Год журнала: 2022, Номер 10(9), С. 2178 - 2178

Опубликована: Сен. 2, 2022

Cardiac fibrosis is a common pathological consequence of most myocardial diseases. It associated with the excessive accumulation extracellular matrix proteins as well fibroblast differentiation into myofibroblasts in cardiac interstitium. This structural remodeling often results dysfunctions such arrhythmias and impaired systolic function patients heart conditions, ultimately leading to failure death. An understanding precise mechanisms still limited due numerous signaling pathways, cells, mediators involved process. review article will focus on pathophysiological processes development fibrosis. In addition, it summarize novel strategies for anti-fibrotic therapies epigenetic modifications, miRNAs, CRISPR technologies various medications cellular animal models.

Язык: Английский

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ALKBH5 ameliorated liver fibrosis and suppressed HSCs activation via triggering PTCH1 activation in an m6A dependent manner

European Journal of Pharmacology, Год журнала: 2022, Номер 922, С. 174900 - 174900

Опубликована: Март 19, 2022

Язык: Английский

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N6-methyladenosine (m6A) RNA modification in fibrosis and collagen-related diseases

Clinical Epigenetics, Год журнала: 2024, Номер 16(1)

Опубликована: Сен. 12, 2024

Язык: Английский

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Roles of Epigenetics in Cardiac Fibroblast Activation and Fibrosis

Cells, Год журнала: 2022, Номер 11(15), С. 2347 - 2347

Опубликована: Июль 30, 2022

Cardiac fibrosis is a common pathophysiologic process associated with numerous cardiovascular diseases, resulting in cardiac dysfunction. fibroblasts (CFs) play an important role the production of extracellular matrix and are essential cell type quiescent state healthy heart. In response to diverse pathologic stress environmental stress, resident CFs convert activated fibroblasts, referred as myofibroblasts, which produce more matrix, contributing fibrosis. Although multiple molecular mechanisms implicated activation fibrosis, there increasing evidence that epigenetic regulation plays key this process. Epigenetics rapidly growing field biology, provides modulated link between pathological stimuli gene expression profiles, ultimately leading corresponding changes. Epigenetic modifications mainly composed three main categories: DNA methylation, histone modifications, non-coding RNAs. This review focuses on recent advances regarding highlights effects activation. Finally, we provide some perspectives prospects for study

Язык: Английский

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Ferroptosis in diabetic cardiomyopathy: Advances in cardiac fibroblast-cardiomyocyte interactions

Heliyon, Год журнала: 2024, Номер 10(15), С. e35219 - e35219

Опубликована: Июль 28, 2024

Diabetic cardiomyopathy (DCM) is a common complication of diabetes, and its pathogenesis remains elusive. Ferroptosis, process dependent on iron-mediated cell death, plays crucial role in DCM via disrupted iron metabolism, lipid peroxidation, weakened antioxidant defenses. Hyperglycemia, oxidative stress, inflammation may exacerbate ferroptosis diabetes. This review emphasizes the interaction between cardiac fibroblasts cardiomyocytes DCM, influencing occurrence. By exploring modulation for potential therapeutic targets, this article offers fresh perspective treatment. The study systematically covers interplay, mechanisms, targeted drugs linked to development.

Язык: Английский

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Regulatory mechanisms of m6A methylation in dilated cardiomyopathy

American Journal of Translational Research, Год журнала: 2025, Номер 17(1), С. 47 - 59

Опубликована: Янв. 1, 2025

Dilated cardiomyopathy (DCM) is a complex heart condition marked by genetic mutations, myocardial dysfunction, and progressive failure. N6-methyladenosine (m6A) methylation, key epigenetic modification, plays crucial role in DCM regulating gene expression various pathologic processes, including cardiomyocyte death, inflammation, fibrosis, mitochondrial dysfunction. m6A modifications influence survival modulating apoptosis, necroptosis, ferroptosis, autophagy-related genes, balancing cellular death pathways. Additionally, m6A-driven regulation of inflammation fibrosis contributes to immune microenvironment stability extracellular matrix remodeling, affecting fibroblast activation stiffness. Mitochondrial health, vital for energy demands, also regulated methylation. Enzymes like methyltransferase-like (METTL) 3 METTL14 promote mitophagy-related expression, while fat mass obesity-associated protein modulates calcium homeostasis, mitigating oxidative stress imbalances. Targeting m6A-related enzymes with small molecules, editing, or RNA interference (RNAi) offers potential tailored therapy. Emerging technologies, such as nanopore m6A-modified mRNA detection, reveal new insight into metabolism, suggesting novel therapeutic avenues. This review underscores methylation pivotal mechanism DCM, providing basis advanced diagnosis

Язык: Английский

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A comprehensive study on the impact of Ligustrum vicaryi L. fruit polysaccharide on myocardial fibrosis through animal experiments, network pharmacology and molecular docking

Frontiers in Cardiovascular Medicine, Год журнала: 2025, Номер 12

Опубликована: Фев. 20, 2025

Myocardial fibrosis (MF) is a prevalent pathological condition associated with various heart diseases, such as failure and arrhythmias, which disrupt electrical signals reduce pumping efficiency. This research explored the therapeutic effects potential mechanisms of Ligustrum vicaryi L. fruit polysaccharide (LVFP) on MF. In vivo experiments, including markers assay, echocardiography, HE staining, Sirius red Masson's trichrome were performed to evaluate efficacy LVFP in treating isoproterenol (ISO)-induced We utilized PharmMapper database identify targets LVFP, aiming explore targets. Additionally, we obtained MF-related from GeneCards database. Venny, bioinformatics tool, intersection between those related STRING construct protein interaction network for overlapping identified key MF through cytoHubba analysis. conducted Gene Ontology (GO) Kyoto Encyclopedia Genes Genomes (KEGG) enrichment analysis also examined using molecular docking techniques. significantly inhibited biomarker hydroxyproline (HYP) decreased myocardial level shown by weight tibia length (HW/TL) measurement when compared ISO-treated mice. it increased ejection fraction (EF) fractional shortening (FS) levels. showed collagen levels mice histological quantification cardiac fibrosis. Based monosaccharide structures 413 identified, 67 Analysis indicated that 9 hub genes (AKT1, HSP90AA1, SRC, GSK3β, VEGFR2, RHOA, ENO1, PKM, IL-2) play roles treatment participating signaling pathways prostate cancer, lipid atherosclerosis, insulin resistance. Molecular results exhibited strong binding VEGFR2 (-8.65 kcal/mol), AKT1 (-7.36 kcal/mol) GSK3β (-7.68 kcal/mol). shows promise agent MF, primarily regulation These findings provide novel insights utilizing LVFP.

Язык: Английский

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