An organ-on-chip model of pulmonary arterial hypertension identifies a BMPR2-SOX17-prostacyclin signalling axis.
Journal
Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179
Informations de publication
Date de publication:
07 11 2022
07 11 2022
Historique:
received:
04
05
2022
accepted:
25
10
2022
entrez:
7
11
2022
pubmed:
8
11
2022
medline:
10
11
2022
Statut:
epublish
Résumé
Pulmonary arterial hypertension (PAH) is an unmet clinical need. The lack of models of human disease is a key obstacle to drug development. We present a biomimetic model of pulmonary arterial endothelial-smooth muscle cell interactions in PAH, combining natural and induced bone morphogenetic protein receptor 2 (BMPR2) dysfunction with hypoxia to induce smooth muscle activation and proliferation, which is responsive to drug treatment. BMPR2- and oxygenation-specific changes in endothelial and smooth muscle gene expression, consistent with observations made in genomic and biochemical studies of PAH, enable insights into underlying disease pathways and mechanisms of drug response. The model captures key changes in the pulmonary endothelial phenotype that are essential for the induction of SMC remodelling, including a BMPR2-SOX17-prostacyclin signalling axis and offers an easily accessible approach for researchers to study pulmonary vascular remodelling and advance drug development in PAH.
Identifiants
pubmed: 36344664
doi: 10.1038/s42003-022-04169-z
pii: 10.1038/s42003-022-04169-z
pmc: PMC9640600
doi:
Substances chimiques
BMPR2 protein, human
EC 2.7.11.30
Bone Morphogenetic Protein Receptors, Type II
EC 2.7.11.30
Epoprostenol
DCR9Z582X0
SOX17 protein, human
0
SOXF Transcription Factors
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1192Subventions
Organisme : British Heart Foundation
ID : FS/15/59/31839
Pays : United Kingdom
Organisme : British Heart Foundation
ID : FS/17/64/33476
Pays : United Kingdom
Organisme : British Heart Foundation
ID : RE/18/4/34215
Pays : United Kingdom
Organisme : British Heart Foundation (BHF)
ID : PG/19/19/34286
Informations de copyright
© 2022. The Author(s).
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