American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Nov 2020
TWIST1 Drives Smooth Muscle Cell Proliferation in Pulmonary Hypertension via Loss of GATA-6 and BMPR2.
Rationale: The bHLH (basic helix-loop-helix) transcription factor TWIST1 (Twist-related protein 1) 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 (SMCs) remains so far unclear. Objectives: To define the role of TWIST1 in SMCs in the pathogenesis of PH. ⋯ Inhibition of TWIST1 promoted the recruitment of GATA-6 to the BMPR2 promoter and restored BMPR2 functional expression. Conclusions: Our findings identify a key role for SMC TWIST1 in the pathogenesis of lung vascular remodeling and in PH that is partially mediated via reduced GATA-6-dependent BMPR2 expression. Inhibition of SMC TWIST1 may constitute a new therapeutic strategy for the treatment of PH.
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Am. J. Respir. Crit. Care Med. · Nov 2020
Editorial CommentA Plot TWIST in Pulmonary Arterial Hypertension.