TWIST1 Drives Smooth Muscle Cell Proliferation in Pulmonary Hypertension via Loss of GATA-6 and BMPR2

American Journal of Respiratory and Critical Care Medicine
Ye FanWolfgang M Kuebler

Abstract

The basic helix-loop-helix transcription factor TWIST1 controls cell proliferation and differentiation in tissue development and disease processes. Recently, endothelial TWIST1 has been linked to pulmonary hypertension (PH) and endothelial-to-mesenchymal transition, yet the role of TWIST1 in smooth muscle cells remains so far unclear. To define the role of TWIST1 in smooth muscle cells (SMC) in the pathogenesis of PH. SMC-specific TWIST1-deficient mice, SMC-specific TWIST1 silencing in rats, mass spectrometry, immunoprecipitation, and chromatin immunoprecipitation were used to delineate the role of SMC TWIST1 in PH. In pulmonary vessels from PH patients and rodent PH models, TWIST1 expression was markedly increased, and predominantly localized to SMCs. SMC-specific TWIST1 deficiency or silencing attenuated the development of PH and distal vessel muscularization in chronic hypoxic mice and monocrotaline-treated rats. In vitro, TWIST1 inhibition or silencing prevented pulmonary artery SMC proliferation and migration. Mechanistically, the observed effects were mediated, at least in part, by TWIST1-dependent degradation of GATA binding protein 6 (GATA-6). Bone morphogenetic protein receptor-2 (BMPR2) was identified as novel downstr...Continue Reading

References

Sep 30, 2006·Circulation Research·Kurt R StenmarkMaria G Frid
Jul 9, 2009·Journal of the American College of Cardiology·Nicholas W MorrellE Kenneth Weir
Jul 9, 2011·The European Respiratory Journal·A M ReynoldsP N Reynolds
Jul 17, 2012·American Journal of Respiratory and Critical Care Medicine·Ly TuChristophe Guignabert
Jan 17, 2015·Circulation·Benoît RanchouxFrédéric Perros
May 10, 2015·The American Journal of Pathology·Robert B GoodAlan M Holmes
Jun 16, 2015·American Journal of Respiratory and Critical Care Medicine·Elaine SoonNicholas W Morrell
Jun 2, 2016·Circulation Research·Marwa M MahmoudPaul C Evans
Feb 10, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jiangning TanDaniel J Kass
Aug 5, 2017·The European Respiratory Journal·Athénaïs BouclyOlivier Sitbon
Aug 31, 2017·Molecular Cancer Research : MCR·Zachary A YochumTimothy F Burns
Sep 16, 2017·American Journal of Respiratory Cell and Molecular Biology·Tadanori MammotoAkiko Mammoto
Nov 3, 2017·American Journal of Respiratory and Critical Care Medicine·Diana ZabiniWolfgang M Kuebler
Jan 24, 2018·The Journal of Pathology·Slaven CrnkovicGrazyna Kwapiszewska
Feb 3, 2018·American Journal of Respiratory and Critical Care Medicine·Olivier BoucheratSébastien Bonnet
May 11, 2018·American Journal of Physiology. Lung Cellular and Molecular Physiology·Ching-Chia WangDavid N Cornfield
Dec 18, 2018·American Journal of Respiratory and Critical Care Medicine·Tatyana NovoyatlevaRalph T Schermuly
Jan 10, 2020·American Journal of Respiratory and Critical Care Medicine·Yuhu HeYing Yu

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Citations

Jul 31, 2020·American Journal of Respiratory and Critical Care Medicine·Kevin Misner, Daniel J Kass
Jan 20, 2021·American Journal of Respiratory and Critical Care Medicine·Li HuFeng Chen

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Methods Mentioned

BETA
SMA
transfection
pull-down
immunoprecipitation
Ubiquitination

Software Mentioned

SPSS
PASW Statistic

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