| Title | Changes in N6-Methyladenosine Modification Modulate Diabetic Cardiomyopathy by Reducing Myocardial Fibrosis and Myocyte Hypertrophy |
| Authors | Ju, Wenhao Liu, Kai Ouyang, Shengrong Liu, Zhuo He, Feng Wu, Jianxin |
| Affiliation | Peking Union Med Coll, Grad Sch, Beijing, Peoples R China Capital Inst Pediat, Dept Biochem & Immunol, Beijing, Peoples R China Beijing China, Beijing Municipal Key Lab Child Dev & Nutriom, Beijing, Peoples R China Peking Univ, Capital Inst Pediatr, Dept Biochem & Immunol, Teaching Hosp, Beijing, Peoples R China Capital Med Univ, Beijing Tongren Hosp, Beijing, Peoples R China |
| Keywords | MESSENGER-RNA NUCLEAR-RNA FOOD-INTAKE YTH DOMAIN FTO GENE M(6)A METHYLATION REVEALS RECOGNITION TRANSLATION |
| Issue Date | 21-Jul-2021 |
| Publisher | FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY |
| Abstract | In this study, we aimed to systematically profile global RNA N6-methyladenosine (m(6)A) modification patterns in a mouse model of diabetic cardiomyopathy (DCM). Patterns of m(6)A in DCM and normal hearts were analyzed via m(6)A-specific methylated RNA immunoprecipitation followed by high-throughput sequencing (MeRIP-seq) and RNA sequencing (RNA-seq). m(6)A-related mRNAs were validated by quantitative real-time PCR analysis of input and m(6)A immunoprecipitated RNA samples from DCM and normal hearts. A total of 973 new m(6)A peaks were detected in DCM samples and 984 differentially methylated sites were selected for further study, including 295 hypermethylated and 689 hypomethylated m(6)A sites (fold change (FC) > 1.5, P < 0.05). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway analyses indicated that unique m(6)A-modified transcripts in DCM were closely linked to cardiac fibrosis, myocardial hypertrophy, and myocardial energy metabolism. Total m(6)A levels were higher in DCM, while levels of the fat mass and obesity-associated (FTO) protein were downregulated. Overexpression of FTO in DCM model mice improved cardiac function by reducing myocardial fibrosis and myocyte hypertrophy. Overall, m(6)A modification patterns were altered in DCM, and modification of epitranscriptomic processes, such as m(6)A, is a potentially interesting therapeutic approach. |
| URI | http://hdl.handle.net/20.500.11897/619570 |
| ISSN | 2296-634X |
| DOI | 10.3389/fcell.2021.702579 |
| Indexed | SCI(E) |
| Appears in Collections: | 首都儿科研究所 |
