Hypoxia Upregulation of BACH1 Aggravates Pulmonary Hypertension Through TGFBR2/SMAD Pathways - PubMed
3 hours ago
- #Pulmonary Hypertension
- #BACH1
- #TGFBR2/SMAD Pathways
- Hypoxia upregulates the transcription factor BACH1 in pulmonary artery smooth muscle cells.
- Under normoxia, BACH1 undergoes prolyl hydroxylation by PHD2, leading to degradation via VHL.
- Hypoxia reduces this hydroxylation, increasing BACH1 stability.
- BACH1 deficiency alleviates pulmonary vascular remodeling, while overexpression exacerbates it.
- Hypoxia causes BACH1 accumulation and recruitment to the TGFBR2 promoter.
- This activates TGFBR2 transcription, enhancing SMAD signaling and extracellular matrix deposition.
- Reducing TGFBR2 expression or inhibiting its kinase activity weakens BACH1-induced effects.
- A TGFBR2 kinase inhibitor blunts BACH1-enhanced pulmonary hypertension development.
- BACH1 inhibition is a potential therapeutic strategy for pulmonary hypertension.