Therapeutic potential of KLF2-induced exosomal microRNAs in pulmonary hypertension
| Autor: | Sandro Satta, Christopher J. Rhodes, Kyeong Beom Jo, Hebah A. Sindi, Martin R. Wilkins, Mai M. Alzaydi, Alexander J. Ainscough, Basma Qazi-Chaudhry, Harm Jan Bogaard, Giusy Russomanno, Beata Wojciak-Stothard, Soni Savai Pullamsetti, Robert Szulcek, Claire Morgan, Roberto Piva, Christina A. Eichstaedt, Ekkehard Grünig, Vahitha B. Abdul-Salam |
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| Přispěvatelé: | Pulmonary medicine, ACS - Pulmonary hypertension & thrombosis, Piccoli, M-T, Saudi Arabian Cultural Bureau, British Heart Foundation, Royal Embassy Of Saudi Arabia, King Abdulaziz City for Science and Technology (KACST) |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine General Physics and Astronomy Exosomes Mice 0302 clinical medicine lcsh:Science Lung Pulmonary Arterial Hypertension Multidisciplinary Middle Aged Cardiovascular diseases medicine.anatomical_structure 030220 oncology & carcinogenesis KLF2 Disease Progression Female Signal Transduction Adult Cell biology Science Primary Cell Culture Mutation Missense Aged Animals Cell Proliferation Disease Models Animal Endothelial Cells Gene Expression Regulation Genetic Therapy Humans Kruppel-Like Transcription Factors MicroRNAs Pulmonary Artery Vascular Remodeling Young Adult General Biochemistry Genetics and Molecular Biology Vascular remodelling in the embryo 03 medical and health sciences ETS1 medicine.artery microRNA medicine Author Correction Animal business.industry General Chemistry medicine.disease Pulmonary hypertension 030104 developmental biology Disease Models Mutation Pulmonary artery Cancer research lcsh:Q Missense business Homeostasis |
| Zdroj: | Nature Communications, 11(1):1185. Nature Publishing Group UK Nature Communications, Vol 11, Iss 1, Pp 1-17 (2020) NATURE COMMUNICATIONS Sindi, H A, Russomanno, G, Satta, S, Abdul-Salam, V B, Jo, K B, Qazi-Chaudhry, B, Ainscough, A J, Szulcek, R, Jan Bogaard, H, Morgan, C C, Pullamsetti, S S, Alzaydi, M M, Rhodes, C J, Piva, R, Eichstaedt, C A, Grünig, E, Wilkins, M R & Wojciak-Stothard, B 2020, ' Therapeutic potential of KLF2-induced exosomal microRNAs in pulmonary hypertension ', Nature Communications, vol. 11, no. 1, 1185 . https://doi.org/10.1038/s41467-020-14966-x Nature Communications |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-020-14966-x |
| 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. |
| Databáze: | OpenAIRE |
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