Author Correction: Therapeutic potential of KLF2-induced exosomal microRNAs in pulmonary hypertension

Autor: Robert Szulcek, Soni Savai Pullamsetti, Basma Qazi-Chaudhry, Christopher J. Rhodes, Hebah A. Sindi, Martin R. Wilkins, Vahitha B. Abdul-Salam, Mai M. Alzaydi, Claire Morgan, Giusy Russomanno, Harm Jan Bogaard, Christina A. Eichstaedt, Ekkehard Grünig, Kyeong Beom Jo, Beata Wojciak-Stothard, Roberto Piva, Alexander J. Ainscough, Sandro Satta
Rok vydání: 2020
Předmět:
Zdroj: Nature Communications
Nature Communications, Vol 11, Iss 1, Pp 1-1 (2020)
ISSN: 2041-1723
Popis: Pulmonary arterial hypertension (PAH) is a severe disorder of lung vasculature that causes right heart failure. Homoeostatic effects of flow-activated transcription factor Krüppel-like factor 2 (KLF2) are compromised in PAH. Here, we show that KLF2-induced exosomal microRNAs, miR-181a-5p and miR-324-5p act together to attenuate pulmonary vascular remodelling and that their actions are mediated by Notch4 and ETS1 and other key regulators of vascular homoeostasis. Expressions of KLF2, miR-181a-5p and miR-324-5p are reduced, while levels of their target genes are elevated in pre-clinical PAH, idiopathic PAH and heritable PAH with missense p.H288Y KLF2 mutation. Therapeutic supplementation of miR-181a-5p and miR-324-5p reduces proliferative and angiogenic responses in patient-derived cells and attenuates disease progression in PAH mice. This study shows that reduced KLF2 signalling is a common feature of human PAH and highlights the potential therapeutic role of KLF2-regulated exosomal miRNAs in PAH and other diseases associated with vascular remodelling.
Pulmonary arterial hypertension is a severe lung disease characterised by progressive vascular remodelling. Here, the authors show that reduced signalling of flow-activated transcription factor KLF2 is a common feature of human PAH and that KLF2-regulated exosomal miRNAs have a therapeutic effect.
Databáze: OpenAIRE
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