Int. J. Mol. Sci. 2017, 18(4), 723; doi:10.3390/ijms18040723
Dysregulated IER3 Expression is Associated with Enhanced Apoptosis in Titin-Based Dilated Cardiomyopathy
1
Department of Cardiology and Cardiovascular Diseases, Eberhard Karls University, 72076 Tübingen, Germany
2
Institute for Integrative Pathophysiology, Universitätsmedizin Mannheim, 68167 Mannheim, Germany
*
Author to whom correspondence should be addressed.
Academic Editor: Anthony Lemarié
Received: 9 January 2017 / Revised: 2 March 2017 / Accepted: 24 March 2017 / Published: 29 March 2017
(This article belongs to the Collection Programmed Cell Death and Apoptosis)
Abstract
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. View Full-TextKeywords:
titin; dilated cardiomyopathy; apoptosis; heart failure; IER3; mouse model
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Zhou, Q.; Hahn, J.K.; Neupane, B.; Aidery, P.; Labeit, S.; Gawaz, M.; Gramlich, M. Dysregulated IER3 Expression is Associated with Enhanced Apoptosis in Titin-Based Dilated Cardiomyopathy. Int. J. Mol. Sci. 2017, 18, 723.
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