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|dc.identifier.citation||Respirology, 2016; 21(3):526-532||-|
|dc.description.abstract||Background and objective: Idiopathic, familial and secondary pulmonary arterial hypertension (PAH) are associated with reduced bone morphogenetic protein receptor type 2 (BMPR2) expression, and in some contexts, TGF-β upregulation. Our aims were to assess BMPR2 gene therapy in a PAH mouse model and to assess the impact on TGF-β signalling. Methods: Using a targeted in vivo gene delivery approach, we assessed the impact of BMPR2 gene delivery in a transgenic mouse model in which PAH was first induced by doxycycline driven expression of a dominant negative BMPR2 mutant (R899X). We also assessed the impact of BMPR2 gene delivery on TGF-β-induced changes in cell signalling in human pulmonary vascular endothelial and smooth muscle cells. Results: In the mouse model, changes in TGF-β levels were not detected, but BMPR2 gene delivery reversed the increase in right ventricle systolic pressure (RVSP) and Fulton Index (FI), associated with a trend to increased pulmonary endothelial nitric oxide synthase (eNOS) gene expression. In vitro, BMPR2 gene transfer reduced TGF-β effects on Smad2, Smad1/5/8 and Erk1/2 phosphorylation in human pulmonary arterial smooth muscle cells (HPASMC). BMPR2 was also found to upregulate nitric oxide (NO) production in lung derived human microvascular endothelial cells (HMVEC-L). Conclusion: This study provides further evidence that BMPR2 modulation may have therapeutic potential.||-|
|dc.description.statementofresponsibility||Feng Feng, Rebecca L Harper and Paul N Reynolds||-|
|dc.rights||© 2015 Asian Pacific Society of Respirology||-|
|dc.subject||Genetics; molecular biology; nitric oxide; pulmonary circulation and pulmonary hypertension||-|
|dc.title||BMPR2 gene delivery reduces mutation-related PAH and counteracts TGF-β-mediated pulmonary cell signalling||-|
|dc.title.alternative||BMPR2 gene delivery reduces mutation-related PAH and counteracts TGF-beta-mediated pulmonary cell signalling||-|
|dc.identifier.orcid||Harper, R. [0000-0003-1465-7372]||-|
|dc.identifier.orcid||Reynolds, P. [0000-0002-2273-1774]||-|
|Appears in Collections:||Aurora harvest 8|
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