Repression of cardiac hypertrophy by KLF15: underlying mechanisms and therapeutic implications
Autor: | Esther E. Creemers, Ingeborg van der Made, Yigal M. Pinto, Monika Hiller, Marinee Chuah, Joost J. Leenders, Wino J. Wijnen, Thierry VandenDriessche, Melissa Swinnen |
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Přispěvatelé: | Amsterdam Cardiovascular Sciences, Cardiology, Medical Biology, Other departments, Division of Gene Therapy & Regenerative Medicine, Cell Biology and Histology |
Rok vydání: | 2011 |
Předmět: |
Oncogene Proteins
Fusion Mouse Cellular differentiation Psychologie appliquée lcsh:Medicine Binding-protein Cardiovascular in-vivo Muscle hypertrophy muscle-cells Mice Molecular cell biology Cardiomyocyte hypertrophy lcsh:Science Promoter Regions Genetic Multidisciplinary GATA4 Angiotensin II Nuclear Proteins Cell Differentiation Animal Models Sciences bio-médicales et agricoles Kruppel-like factor Cell biology Extracellular Matrix DNA-Binding Proteins Connective Tissue COS Cells Hypertension cardiovascular system Medicine Biologie serum response factor Research Article Mef2 medicine.medical_specialty Gene-espression DNA transcription Kruppel-Like Transcription Factors Cardiomegaly Biology Cell Growth Model Organisms Internal medicine Serum response factor medicine Genetics Animals Humans myocardin Transcription factor Heart Failure Binding Sites lcsh:R Genetic Therapy Disease Models Animal Endocrinology Gene Expression Regulation Myocardin Trans-Activators lcsh:Q Mutant Proteins Gene expression Transcription Factors |
Zdroj: | PLoS ONE PLoS ONE, 7(5). Public Library of Science PLoS ONE, Vol 7, Iss 5, p e36754 (2012) PloS one, 7 (5 |
ISSN: | 1932-6203 |
Popis: | The Kruppel-like factor (KLF) family of transcription factors regulates diverse cell biological processes including proliferation, differentiation, survival and growth. Previous studies have shown that KLF15 inhibits cardiac hypertrophy by repressing the activity of pivotal cardiac transcription factors such as GATA4, MEF2 and myocardin. We set out this study to characterize the interaction of KLF15 with putative other transcription factors. We first show that KLF15 interacts with myocardin-related transcription factors (MRTFs) and strongly represses the transcriptional activity of MRTF-A and MRTF-B. Second, we identified a region within the C-terminal zinc fingers of KLF15 that contains the nuclear localization signal. Third, we investigated whether overexpression of KLF15 in the heart would have therapeutic potential. Using recombinant adeno-associated viruses (rAAV) we have overexpressed KLF15 specifically in the mouse heart and provide the first evidence that elevation of cardiac KLF15 levels prevents the development of cardiac hypertrophy in a model of Angiotensin II induced hypertrophy. © 2012 Leenders et al. SCOPUS: ar.j info:eu-repo/semantics/published |
Databáze: | OpenAIRE |
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