Identification of TGF-ß-related genes in cardiac hypertrophy and heart failure based on single cell RNA sequencing.
Aging (Albany NY)
; 15(14): 7187-7218, 2023 07 26.
Article
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| MEDLINE
| ID: mdl-37498303
BACKGROUND: Heart failure (HF) remains a huge medical burden worldwide. Pathological cardiac hypertrophy is one of the most significant phenotypes of HF. Several studies have reported that the TGF-ß pathway plays a double-sided role in HF. Therefore, TGF-ß-related genes (TRGs) may be potential therapeutic targets for cardiac hypertrophy and HF. However, the roles of TRGs in HF at the single-cell level remain unclear. METHOD: In this study, to analyze the expression pattern of TRGs during the progress of cardiac hypertrophy and HF, we used three public single-cell RNA sequencing datasets for HF (GSE161470, GSE145154, and GSE161153), one HF transcriptome data (GSE57338), and one hypertrophic cardiomyopathy transcriptome data (GSE141910). Weighted gene co-expression network analysis (WGCNA), functional enrichment analysis and machine learning algorithms were used to filter hub genes. Transverse aortic constriction mice model, CCK-8, wound healing assay, quantitative real-time PCR and western blotting were used to validate bioinformatics results. RESULTS: We observed that cardiac fibroblasts (CFs) and endothelial cells showed high TGF-ß activity during the progress of HF. Three modules (royalblue, brown4, and darkturquoize) were identified to be significantly associated with TRGs in HF. Six hub genes (TANC2, ADAMTS2, DYNLL1, MRC2, EGR1, and OTUD1) showed anomaly trend in cardiac hypertrophy. We further validated the regulation of the TGF-ß-MYC-ADAMTS2 axis on CFs activation in vitro. CONCLUSIONS: This study identified six hub genes (TANC2, ADAMTS2, DYNLL1, MRC2, EGR1, and OTUD1) by integrating scRNA and transcriptome data. These six hub genes might be therapeutic targets for cardiac hypertrophy and HF.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Factor de Crecimiento Transformador beta
/
Insuficiencia Cardíaca
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Aging (Albany NY)
Asunto de la revista:
GERIATRIA
Año:
2023
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
Estados Unidos