Journal article
Authors list: Sindi, Hebah A.; Russomanno, Giusy; Satta, Sandro; Abdul-Salam, Vahitha B.; Jo, Kyeong Beom; Qazi-Chaudhry, Basma; Ainscough, Alexander J.; Szulcek, Robert; Bogaard, Harm Jan; Morgan, Claire C.; Pullamsetti, Soni S.; Alzaydi, Mai M.; Rhodes, Christopher J.; Piva, Roberto; Eichstaedt, Christina A.; Gruenig, Ekkehard; Wilkins, Martin R.; Wojciak-Stothard, Beata
Publication year: 2020
Journal: Nature Communications
Volume number: 11
Issue number: 1
ISSN: 2041-1723
Open access status: Gold
DOI Link: https://doi.org/10.1038/s41467-020-14966-x
Publisher: Nature Research
Abstract:
Pulmonary arterial hypertension (PAH) is a severe disorder of lung vasculature that causes right heart failure. Homoeostatic effects of flow-activated transcription factor Kruppel-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-181a5p 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.
Citation Styles
Harvard Citation style: Sindi, H., Russomanno, G., Satta, S., Abdul-Salam, V., Jo, K., Qazi-Chaudhry, B., et al. (2020) Therapeutic potential of KLF2-induced exosomal microRNAs in pulmonary hypertension, Nature Communications, 11(1), Article 1185. https://doi.org/10.1038/s41467-020-14966-x
APA Citation style: Sindi, H., Russomanno, G., Satta, S., Abdul-Salam, V., Jo, K., Qazi-Chaudhry, B., Ainscough, A., Szulcek, R., Bogaard, H., Morgan, C., Pullamsetti, S., Alzaydi, M., Rhodes, C., Piva, R., Eichstaedt, C., Gruenig, E., Wilkins, M., & Wojciak-Stothard, B. (2020). Therapeutic potential of KLF2-induced exosomal microRNAs in pulmonary hypertension. Nature Communications. 11(1), Article 1185. https://doi.org/10.1038/s41467-020-14966-x
Keywords
ARTERIAL-HYPERTENSION; ENDOTHELIAL-GROWTH-FACTOR; KLF2; KRUPPEL-LIKE FACTOR; SMOOTH-MUSCLE
