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Lookup NU author(s): Emerita Professor Helen ArthurORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© The Author(s) 2025. Endoglin (ENG) is a single-pass transmembrane protein highly expressed in vascular endothelial cells (ECs), where it plays fundamental roles in EC functions. ENG is implicated in several cardiovascular disorders including hereditary haemorrhagic telangiectasia, pulmonary arterial hypertension (PAH) and preeclampsia. However, molecular mechanisms underlying ENG function are not fully understood. Initially identified as a co-receptor for TGF-β signalling, ENG’s extracellular domain was later found to only bind BMP9 and BMP10 with high affinity. The relationship between these two observations is unclear. Here, we provide evidence for two primary functions of co-receptor ENG. First, ENG efficiently displaces prodomains from BMP9 and BMP10, enabling effective capturing of both ligands from the circulation. Second, ENG binds to and recruits TGFBRII into the BMP9 signalling complex, thereby explaining ENG’s involvement in both TGF-β and BMP9 pathways. We identify BMP9 target genes NOG and ADAMTSL2 as preferentially dependent on ENG and show that their transcript levels have strong positive correlation with ENG in human lung tissues; the expression levels of all three genes are significantly reduced in PAH. Our findings address an important gap in our understanding on ENG biology and provide crucial insight for therapeutic targeting these pathways in vascular diseases.
Author(s): Guo J, Kostrzynska K, Kamzolas I, Yang X, Thorikay M, De Bie E, Jones RJ, Brownstein A, Long L, Rhodes CJ, Lawrie A, Wilkins MR, Groeneveld E, Tong Z, Goumans M-J, Petsalaki E, Hong J, Toshner MR, Vidal-Puig A, Arthur HM, Li W
Publication type: Article
Publication status: Published
Journal: Nature Communications
Year: 2026
Volume: 17
Online publication date: 31/12/2025
Acceptance date: 27/11/2025
Date deposited: 02/02/2026
ISSN (electronic): 2041-1723
Publisher: Springer Nature
URL: https://doi.org/10.1038/s41467-025-67531-9
DOI: 10.1038/s41467-025-67531-9
Data Access Statement: The data generated in this study are provided in the Supplementary Information and Source Data file. All antibodies and qPCR primers can be found in the Supplementary Data 1. The RNAseq dataset generated in this study has been deposited in the NCBI Gene Expression Omnibus database under accession code GSE289309. Links to data used in this study are as follows: 5HZW. 3KFD. 4YCG. 7POI. 4FAO. 7PPC. GSE289309. GSE113439. Sharing request for newly generated materials in this study can be sent to the corresponding author. Source data are provided with this paper.
PubMed id: 41476036
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