Pulmonary vascular disease & thromboembolism
Hypoxia Upregulation of BACH1 Aggravates Pulmonary Hypertension Through TGFBR2/SMAD Pathways
Authors' conclusion
Our study illustrates that BACH1 is prolyl-hydroxylated in an oxygen/PHD-dependent manner, affecting its stability through VHL. BACH1 is crucial for hypoxia-induced PH by activating TGFBR2/SMAD in smooth muscle cells.
Study context
- Population
- PASMCs, rodent pulmonary hypertension (PH) models and lung specimens from patients with idiopathic PAH
Main finding
As reported in the abstract
- BACH1 upregulated in lung tissue and PASMCs from patients with idiopathic PAH and animals with experimental PH
- Under normoxia, PHD2-mediated prolyl hydroxylation of BACH1 facilitated its degradation by VHL; hypoxia decreased this hydroxylation, increasing BACH1 protein stability
- Smooth muscle BACH1 deficiency or overexpression in mice alleviated or exacerbated pulmonary vascular remodelling and hypoxia-induced PH
- Hypoxia-accumulated BACH1 recruited to TGFBR2 promoter, activating TGFBR2 transcription, SMAD signalling and extracellular matrix deposition
- Decreased TGFBR2 expression or inhibited kinase activity significantly attenuated BACH1-induced extracellular matrix genes
- BACH1-enhanced PH development blunted by a TGFBR2 kinase inhibitor
Original publication
Hypoxia Upregulation of BACH1 Aggravates Pulmonary Hypertension Through TGFBR2/SMAD Pathways. Circulation. Published 26 May 2026. doi:10.
Summarised from the published abstract; every number is checked against it