Dysregulated IER3 expression is associated with enhanced apoptosis in titin-based dilated cardiomyopathy
Apoptosis (type I programmed cell death) of cardiomyocytes is a major process that plays a role in the progression of heart failure. The early response gene IER3 regulates apoptosis in a wide variety of cells and organs. However, its role in heart failure is largely unknown. Here, we investigate the...
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| Main Authors: | , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
29 March 2017
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| In: |
International journal of molecular sciences
Year: 2017, Volume: 18, Issue: 4 |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms18040723 |
| Online Access: | Verlag, kostenfrei, Volltext: http://dx.doi.org/10.3390/ijms18040723 Verlag, kostenfrei, Volltext: http://www.mdpi.com/1422-0067/18/4/723 
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| Author Notes: | Qifeng Zhou, Julia Kelley Hahn, Balram Neupane, Parwez Aidery, Siegfried Labeit, Meinrad Gawaz and Michael Gramlich |
| Summary: | Apoptosis (type I programmed cell death) of cardiomyocytes is a major process that plays a role in the progression of heart failure. The early response gene IER3 regulates apoptosis in a wide variety of cells and organs. However, its role in heart failure is largely unknown. Here, we investigate the role of IER3 in an inducible heart failure mouse model. Heart failure was induced in a mouse model that imitates a human titin truncation mutation we found in a patient with dilated cardiomyopathy (DCM). Transferase dUTP nick end labeling (TUNEL) and ssDNA stainings showed induction of apoptosis in titin-deficient cardiomyocytes during heart failure development, while IER3 response was dysregulated. Chromatin immunoprecipitation and knock-down experiments revealed that IER3 proteins target the promotors of anti-apoptotic genes and act as an anti-apoptotic factor in cardiomyocytes. Its expression is blunted during heart failure development in a titin-deficient mouse model. Targeting the IER3 pathway to reduce cardiac apoptosis might be an effective therapeutic strategy to combat heart failure. |
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| Item Description: | Published: 29 March 2017 Gesehen am 09.08.2018 |
| Physical Description: | Online Resource |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms18040723 |