In this section
@article{Toe:2026:10.1002/pul2.70272,
author = {Toe, QK and Issitt, T and Quinlan, GJ and John, Wort S},
doi = {10.1002/pul2.70272},
journal = {Pulm Circ},
title = {The Interplay Between IL-6, Hepcidin, and BMPR2 Signalling in Pulmonary Arterial Hypertension: Mechanistic Insights Into Vascular Remodelling.},
url = {http://dx.doi.org/10.1002/pul2.70272},
volume = {16},
year = {2026}
}
TY - JOUR
AB - Pulmonary arterial hypertension (PAH) is characterized by excessive pulmonary vasoconstriction and vascular remodelling, with mutations in bone morphogenetic protein receptor type 2 (BMPR2) being the most common genetic alteration associated with the disease. While inflammatory mediators like interleukin-6 (IL-6) and the iron-regulatory hormone hepcidin have been implicated in vascular remodelling, their interaction with BMPR2 signalling remains poorly understood. This study investigated how IL-6 and hepcidin influence BMPR2 expression and downstream signalling in human pulmonary arterial endothelial cells (hPAECs). Using qPCR and Western blot analyses, we demonstrated that both IL-6 and hepcidin significantly reduced BMPR2 mRNA and protein levels in hPAECs. Intriguingly, despite this reduction, SMAD1/5 phosphorylation remained active, suggesting compensatory signalling through alternative receptor complexes. Treatment with IL-6 and hepcidin upregulated inhibitors of differentiation (ID) protein expression, mimicking the effects observed with BMPR2 knockdown. These findings reveal a novel regulatory axis involving IL-6, hepcidin, and BMPR2 in PAH pathogenesis, where IL-6 and hepcidin promote vascular remodelling through both BMPR2-dependent and independent mechanisms. These results suggest that therapeutic strategies targeting this axis, particularly those aimed at rebalancing BMP/TGF-β signalling, may hold promise for treating PAH.
AU - Toe,QK
AU - Issitt,T
AU - Quinlan,GJ
AU - John,Wort S
DO - 10.1002/pul2.70272
PY - 2026///
SN - 2045-8932
TI - The Interplay Between IL-6, Hepcidin, and BMPR2 Signalling in Pulmonary Arterial Hypertension: Mechanistic Insights Into Vascular Remodelling.
T2 - Pulm Circ
UR - http://dx.doi.org/10.1002/pul2.70272
UR - https://www.ncbi.nlm.nih.gov/pubmed/41948512
VL - 16
ER -