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Published on: June 3, 2018
Herpud1 suppress angiotensin II induced hypertrophy in cardiomyocytes
Mei Mikawa1, Chihiro Sakai1, Takeshi Yamamoto1
1Department of Laboratory Medicine, Faculty of Health Sciences, Yamaguchi University Graduate School of Medicine, 1-1-1 Minamikogushi, Ube, Yamaguchi, 755-8505, Japan.
Insights
Homocysteine-responsive endoplasmic reticulum-resident ubiquitin-like domain member 1 (Herpud1) acts as an anti-hypertrophic gene. Suppressing Herpud1 promotes cardiomyocyte hypertrophy, while its overexpression inhibits angiotensin II-induced hypertrophy.
Area of Science:
- Cardiovascular Biology
- Molecular Cardiology
- Gene Function Studies
Background:
- Cardiomyocyte hypertrophy is a significant risk factor for heart failure.
- The endoplasmic reticulum stress response plays a role in cardiac remodeling.
- Understanding novel gene regulators is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the role of the Herpud1 gene in the development of cardiomyocyte hypertrophy.
- To determine if Herpud1 acts as a protective or detrimental factor in cardiac hypertrophy.
Main Methods:
- Utilized H9C2 rat cardiomyocyte cell lines for experimental manipulation.
- Employed small interfering RNA (siRNA) to suppress Herpud1 expression.
- Overexpressed Herpud1 using GFP-plasmid transfection.
- Assessed Herpud1 protein levels and cell hypertrophy via immunostaining.
- Analyzed the nuclear translocation of NFATc4, a key transcription factor.
Main Results:
- Herpud1 siRNA transfection led to decreased Herpud1 protein expression and reduced hypertrophy.
- Overexpression of Herpud1 effectively suppressed angiotensin II-induced cardiomyocyte hypertrophy.
- Herpud1 overexpression inhibited the nuclear translocation of NFATc4.
Conclusions:
- Herpud1 demonstrates anti-hypertrophic properties in cardiomyocytes.
- Herpud1 may serve as a therapeutic target for preventing or treating cardiac hypertrophy.
- The findings suggest Herpud1 is a protective gene against angiotensin II-induced cardiac remodeling.
Purpose:
The purpose of this study was to analyze the role of homocysteine-responsive endoplasmic reticulum-resident ubiquitin-like domain member 1 (Herpud1) gene in the development of cardiomyocyte hypertrophy.
Method:
In order to examine the effect of suppressing Herpud1 expression, Herpud1 small interfering RNA (siRNA) was introduced into H9C2 cells, which are cell lines derived from rat myocardium, and the degree of Herpud1 protein expression and cell hypertrophy in the Herpud1 siRNA-transfected group and the control group was compared by immunostaining 48 h after Herrpud1 siRNA introduction. To examine whether hypertrophy induced by angiotensin II (Ang II) can be suppressed by the overexpression of Herpud1, the green fluorescent protein (GFP)-Herpud1 plasmid was introduced into H9C2 cells, and the degree of cell hypertrophy was examined in the GFP-Herpud1-and control groups for 48 h. Nuclear translocation of nuclear factor of activated T-cells, cytoplasmic 4 (NFATc4), a transcription factor for hypertrophic genes, was also examined.
Results:
[1] Herpud1 siRNA-transfected cells showed decreased Herpud1 protein expression and hypertrophy formation compared to control cells [2]; Overexpression of Herpud1 suppresses Ang II-induced cell hypertrophy; and [3] Overexpression of Herpud1 inhibits nuclear translocation of NFATc4.
Discussion:
It was suggested that Herpud1 might be an anti-hypertrophic gene in Ang II induced cardiomyocytes hypertrophy.
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