METTL3 in Diabetic Cardiomyopathy
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE252044 | GEO | 2025/12/25
REPOSITORIES: GEO
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Project description:To investigate the role of NAT10 in diabetic cardiomyopathy in response to exercise, 6-week-old NAT10 floxed mice were fed a high-fat diet (HFD) for 18 weeks followed by low doses of STZ injections, some of the mice were then injected with AAV9-cTnT-Cre to knockout NAT10 in cardiomyocytes. There mice were then subjected to either sedentary or eight weeks of treadmill exercise. We then performed gene expression profiling analysis using data obtained from RNA-seq from RNAs pulldown with an ac4C antibody.
2025-06-01 | GSE291716 | GEO
Project description:In this study we sought to determine how hepatocyte-specific PPARgamma expression regulates hepatic gene expression in normal (healthy) mice fed a LFCF diet, or mice that were fed a HFCF diet for 24 weeks to induce non-alcoholic steatohepatitis (NASH). Specifically, we used chow-fed adult (10 week-old) PPARgamma floxed male mice and injected them with AAV8-TBG-Cre to knockout PPARgamma in hepatocytes (KO). A subset of PPARgamma floxed mice were injected with AAV8-TBG-Null to generate controls (C). Two weeks after AAV injections, half of the mice in each group were fed a low fat, cholesterol and fructose (LFCF) diet, or a high fat, cholesterol and fructose (HFCF) diet for 24 weeks. Livers were collected at the end of the study to assess hepatic gene expression with RNA-seq (performed by Novogen, Inc.)
2021-01-15 | GSE162249 | GEO
Project description:Diabetic cardiomyopathy (DCM) is an important complication of chronic diabetes mellitus (DM). However, its pathogenesis and pathologic process have not been fully elucidated. This study was aimed to investigate the role of ferroptosis in the pathogenesis of DCM and clarify the effect of HMOX1 on DCM by targeting ferroptosis. DCM mouse model was constructed by high fat diet (HFD) feeding and streptozotocin (STZ). injection.
2023-08-28 | GSE241166 | GEO
Project description:The study investigates the effect of a heterozygous MYBPC3 mutation combined with Western diet feeding on protein expression in a HCM mouse model. Hypertrophic cardiomyopathy (HCM) is the most common inherited genetic heart disease, characterized by asymmetric left ventricular hypertrophy and diastolic dysfunction. It is generally accepted that HCM is caused by mutations in genes encoding sarcomere proteins (e.g. MYBPC3, MYH7). However, not all mutation carriers will develop HCM and, moreover, phenotypical variation in terms of clinical presentation is large. The phenotypical expression of HCM thus requires additional disease modifiers on top of a sarcomere gene mutation. Clinical reports identify obesity and related comorbidities (diabetes, hyperlipidemia, hypertension) as a major factor contributing to disease expression and severity. We aimed to mimic this situation in a HCM mouse model by feeding a Western diet (8 weeks) to mice carrying a heterozygous mutation in MYBPC3. These heterozygous mice are phenotype negative under normal conditions, but developed cardiac dysfunction and hypertrophy upon Western diet feeding. The main goal of this proteomic screening is to identify clusters of proteins and pathways that are down/upregulated specifically in the left ventricle of mice suffering from a mutation and Western diet feeding. Also, we are interested in protein expression differences caused solely by mutation or Western diet. Group 1 are Wild type mice that received normal chow; group 2 are heterozygous mice that received normal chow; group 3 are Wild type mice that received a Western diet; group 4 are heterozygous mice that received a Western diet.
2023-10-01 | PXD043345 | Pride
Project description:Background: N6-methyladenosine (m6A) RNA modification plays a crucial role in various biological events and is implicated in various metabolic-related diseases. However, its role in MASLD remains unclear. This study aims to investigate the impact of Mettl3 on MASLD through multi-omics analysis, with a focus on exploring its potential mechanisms of action. Methods: MASLD mouse models were established by feeding a high-fat diet for 12 weeks, and Mettl3 stable overexpression AML12 cell models were constructed via lentiviral transfection. Subsequent transcriptomic and proteomic analyses, as well as integrated analysis between different omics datasets, were conducted. Results: Mettl3 expression significantly increased in MASLD mouse models. In the transcriptomic and proteomic analyses, we identified 848 genes with significant inconsistencies between transcriptomic and proteomic datasets. GO/KEGG enrichment terms may involve post-transcriptional modifications, particularly Mettl3-mediated m6A modification. Subsequently, through integrated proteomic analysis of Mettl3-overexpressed AML12 cell models and MASLD mouse models, we selected the top 20 co-upregulated and co-downregulated GO/KEGG terms as the main biological processes influenced by Mettl3 in MASLD. By intersecting with pathways obtained from previous integrated analyses, we identified GO/KEGG terms affected by Mettl3-induced m6A modification. Protein-protein interaction analysis of proteins involved in these pathways highlighted GAPDH, ENO1, and TPI1 as three key hub genes. Conclusion: In MASLD, Mettl3 regulates the glycolytic pathway through m6A modification, influencing the occurrence and development of the disease via the key hub genes GAPDH, ENO1, and TPI1. These findings expand our understanding of MASLD and provide strong evidence for potential therapeutic targets and drug development.
2024-09-20 | PXD050565 | Pride
Project description:The main cause of morbidity and mortality in diabetes mellitus (DM) are cardiovascular complications. Diabetic cardiomyopathy (DCM) remains incompletely understood. Animal models have been crucial in exploring DCM pathophysiology while identifying potential therapeutic targets. Streptozotocin (STZ) has been widely used to produce experimental models of both type 1 and type 2 DM (T1DM and T2DM). Here we compared these two models for their effects on cardiac structure, function, and transcriptome. Different doses of STZ and different diet chows were used to generate T1DM and T2DM in C57BL/6J mice. Normal euglycemic and non-obese sex and age-matched mice served as controls (CTRL). Immunohistochemistry, RT-PCR, and RNA-Seq were employed to compare hearts from the three animal groups. STZ-induced T1DM and T2DM differently affect left ventricular function and myocardial performance. T1DM displays an exaggerated apoptotic cardiomyocyte (CM) death and reactive hypertrophy and fibrosis along with increased cardiac oxidative stress, CM DNA damage and senescence when compared to T2DM mice. T1DM and T2DM differently affect whole cardiac transcriptome. In conclusion, STZ-induced T1DM and T2DM mouse models show significant differences in cardiac remodeling, function and whole transcriptome. These differences could be of key relevance when choosing an animal model to study specific features of DCM.
2023-02-20 | E-MTAB-12558 | biostudies-arrayexpress
Project description:It has been recently reported that the patients with non-alcoholic fatty liver diseases (NAFLD) had accompanied with cardiac dysfunction. However, an animal model of steatohepatitis related cardiomyopathy has not been reported. In the current study, we have developed a mouse model of steatohepatitis-related cardiomyopathy and examined whether a selective PPARα modulator, pemafibrate would improve both steatohepatitis and cardiomyopathy. C57Bl/6 male mice were fed 1. normal chow diet (C group), 2. high fat/high cholesterol/high sucrose/bile acid diet (N group), or 3. N with pemafibrate 0.1 mg/kg (NP group) for three or eight weeks, respectively. Cardiac function was evaluated by ultra-high magnetic field 7-Tesla magnetic resonance imaging (7T-MRI). Even at the eight weeks, we have detected cholesterol crystals, free cholesterol accumulation in liver, followed by macrophage infiltration and fibrosis as wells as activation of NLRP3, caspase-1 and IL-1βmRNA. At the same time in heart, the ratio of heart to body was increased in N group compared to C group. Left ventricular (LV) ejection fraction (LVEF) was moderately decreased in N group compared to C group (50.2±2.8 vs 59.8±2.1, p<0.05). LV circumferential strain and radial strain are focally attenuated in N group, suggesting the early lesion of myocardial damages. mRNA expression of Nlrp3, Caspase1 and Il1b were enhanced in N group, followed by increased protein levels of Caspase-1 and Asc. Rna-sequence analysis revealed that NOD-like receptor and PI3 kinase-AKT pathways were up-regulated, suggesting hypertrophic phenotypes. in N group. Importantly, NLRP3 inflammasome activation were suppressed both in liver and heart in NP group, suggesting pemafibrate had the beneficial effect on steatohepatitis and cardiomyopathy. In addition, four week treatment by pemafibrate improved steatohepatitis and cardiomyopathy after development for eight week. We have first developed the animal model of steatohepatitis-related cardiomyopathy, characterized by the activation of NLRP3 inflammasome pathway both in liver and heart. Steatohepatitis-related cardiomyopathy displayed moderate reduction of LVEF and focal impairment of LV strain by 7T-MRI. Pemafibrate suppressed steatohepatitis, hepatic fibrosis and cardiomyopathy.
2022-02-23 | GSE175708 | GEO
Project description:we find METTL3 associates with polyribosomes and promotes translation. METTL3 depletion inhibits translation, and both wild-type and catalytically inactive METTL3 promote translation when tethered to the 3' untranslated region (UTR) of a reporter mRNA. Mechanistically, METTL3 enhances mRNA translation through an interaction with the translation initiation machinery. m6A seq in A549 and H1299 cells, RNA seq in METTL3 knockdown cells
2016-07-03 | E-GEOD-76367 | biostudies-arrayexpress
Project description:The lack of an appropriate preclinical model of non-alcoholic fatty liver disease (NAFLD) that recapitulates the whole disease spectrum impedes exploration of disease pathophysiology and the development of effective treatment strategies. Therefore, we developed new mose model with Streptozotocin (STZ)and high-fat diet (HFD). In breif, male C57BL/6J mice were injected with low-dose streptozotocin (40 mg/kg) for 5 consecutive days beginning at 7 weeks of age and subsequently fed a high-fat diet from week 8 (STZ+HFD) onwards. Hepatic histopathology, transcriptomics, epigenetics, and metabolic phenotypes were evaluated at various time-points. The hepatic transcriptomes of STZ+HFD mice and NAFLD patients with similar liver histopathology were compared. In STZ+HFD mice, dietary changes from HFD to standard chow and administration of tirzepatide, a dual glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 receptor agonist, were introduced to assess the therapeutic efficacy of these interventions. STZ+HFD mice gradually developed fatty liver, non-alcoholic steatohepatitis (NASH), hepatic fibrosis, and hepatocellular carcinoma (HCC) in the context of metabolic dysfunction. In particular, from 32 weeks of age, NASH and advanced fibrosis were evident. At 38 weeks, a proportion of STZ+HFD mice developed HCC, which was subsequently observed in all mice up to 68 weeks of age. Furthermore, the hepatic transcriptomic features of STZ+HFD mice closely reflected those of patients with NASH and NAFLD-related HCC. Notably, dietary changes and tirzepatide administration alleviated NASH, hepatic fibrosis, and hepatic tumorigenesis in STZ+HFD mice. Put together, we established a murine model recapitulating the main histopathologic, transcriptomic, and metabolic alterations observed in NAFLD patients with metabolic dysfunction was successfully established.
2024-06-17 | GSE246213 | GEO
Project description:To gain insight into possible processes that require m6A for their function, METTL3 was knocked down (KD) in HepG2 cells by siRNA transfections Differential expression analysis of METTL3 KD versus mock-transfected HepG2 cells, in 2 biological replicates
2012-04-25 | E-GEOD-37001 | biostudies-arrayexpress