期刊
LIFE SCIENCES
卷 292, 期 -, 页码 -出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2021.119552
关键词
Heart failure; Histone deacetylase 3; DNA methyltransferase 1; Src homology domain 2-containing tyrosine; phosphatase-1; Methylation; Acetylation
资金
- Ningxia Provincial Natural Science Foundation Project [2020A0227]
- Individual Innovation and Entrepreneurship Project for Overseas Students in Ningxia Hui Autonomous Region
This study aimed to explore the regulatory mechanism of histone deacetylase 3 (HDAC3) and DNA methyltransferase 1 (DNMT1)/Src homology domain 2-containing tyrosine phosphatase-1 (SHP-1) axis in heart failure (HF). The study found that HDAC3 modified DNMT1 through deacetylation to suppress SHP-1 expression, which in turn led to the development of cardiomyocyte hypertrophy-induced HF. This provides potential therapeutic targets for HF treatment.
Aims: Heart failure (HF) is a progressive disease with recurrent hospitalizations and high mortality. However, the mechanisms underlying HF remain unclear. The present study aimed to explore the regulatory mechanism of histone deacetylase 3 (HDAC3) and DNA methyltransferase 1 (DNMT1)/Src homology domain 2-containing tyrosine phosphatase-1 (SHP-1) axis in HF.Methods: The HF rat models and hypertrophy cell models were established. The characteristic parameters of the heart were detected by echocardiography. A multichannel physiological signal acquisition system was used to detect the hemodynamic parameters. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression of HDAC3, DNMT1, and SHP-1 mRNAs, while Western blot was applied to analyze the expression of proteins. Masson staining was used to analyze the degree of collagen fiber infiltration. TdTmediated DUTP nick end labeling (TUNEL) staining was performed to analyze the apoptosis of myocardial tissue cells. Co-immunoprecipitation (co-IP) was conducted to study the interaction between HDAC3 and DNMT1. Flow cytometry was used to analyze the apoptosis.Key findings: HDAC3 and DNMT1 were highly expressed in HF rat and hypertrophy cell models. HDAC3 modified DNMT1 through deacetylation to inhibit ubiquitination-mediated degradation, which promoted the expression of DNMT1. DNMT1 inhibited SHP-1 expression via methylation in the promoter region. In summary, HDAC3 modified DNMT1 by deacetylation to suppress SHP-1 expression, which in turn led to the development of cardiomyocyte hypertrophy-induced HF.Significance: This study provided potential therapeutic targets for HF treatment.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据