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
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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