BMP9 Modulates IL-33 Signaling to Mitigate EndMT in Pulmonary Arterial Hypertension

Area of Science:

• Cardiovascular Biology
• Pulmonary Medicine
• Molecular Signaling

Background:

• Pulmonary arterial hypertension (PAH) involves disrupted bone morphogenetic protein (BMP) signaling, inflammation, and endothelial-to-mesenchymal transition (EndMT).
• Interleukin-33 (IL-33) signaling is implicated in PAH progression by promoting EndMT and interacting with BMP9.

Purpose of the Study:

• To investigate the role of IL-33 signaling in PAH.
• To determine the interaction between IL-33 and BMP9 in the context of EndMT.
• To explore potential therapeutic strategies targeting the IL-33 pathway.

Main Methods:

• Assessed IL-33 expression in mouse models and human PAH tissues.
• Analyzed EndMT and signaling pathways in endothelial cells exposed to IL-33, BMP9, and sST2.
• Quantified plasma BMP9 and sST2 levels in PAH patients.

Main Results:

• Elevated IL-33 expression was observed in PAH.
• BMP9 upregulated sST2, inhibited IL-33 target genes, and suppressed IL-33-induced EndMT.
• Circulating BMP9 and sST2 levels correlated in specific PAH patient groups.

Conclusions:

• BMP9 exerts a protective effect against IL-33-induced EndMT in pulmonary arterial endothelial cells.
• BMP9 upregulates sST2 and neutralizes IL-33, mitigating EndMT.
• Targeting the IL-33 signaling pathway presents a promising therapeutic avenue for PAH.