Repression of cardiac hypertrophy by KLF15: underlying mechanisms and therapeutic implications.

PloS One
Joost J LeendersEsther E Creemers

Abstract

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.

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Citations

Oct 27, 2012·Expert Review of Cardiovascular Therapy·Michelle KrekeEduardo Marbán
Jan 9, 2017·Cardiovascular Drugs and Therapy·Russell G Rogers, Jeffrey S Otis
Mar 2, 2017·Development·Agnieszka B BialkowskaSandeep K Mallipattu
Nov 6, 2018·Canadian Journal of Physiology and Pharmacology·Ryan WangRushita A Bagchi
May 6, 2019·Physiological Reports·Catherine BeaumontJacques Couet
Jul 7, 2019·Cardiovascular Diabetology·Golam M UddinGary D Lopaschuk
May 16, 2018·Cardiovascular Endocrinology & Metabolism·Yang YupingZhou Qing
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Apr 28, 2018·International Journal of Molecular Sciences·Sheila K PatelLouise M Burrell
Jan 11, 2020·Molecular Medicine Reports·Shu-Fan ZouLin Chen
Mar 19, 2020·International Journal of Molecular Medicine·Jin ZhouRudan Zhou
Jun 30, 2018·Molecular Medicine Reports·Bing LiuHaofu Wang

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Methods Mentioned

BETA
pulldown
PCR
fluorescence microscopy

Software Mentioned

Scion Image

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