Thrombin cleaves membrane-bound endoglin potentially contributing to the heterogeneity of circulating endoglin in preeclampsia
Increased levels of soluble endoglin (sEng) are found in serum, plasma, and urine of preeclampsia patients. sEng is released from membrane-bound endoglin through the proteolytic activity of metalloproteases, but its structural heterogeneity suggests the involvement of additional proteases. Considering the roles of thrombin and sEng in preeclampsia pathogenesis, we investigated whether thrombin cleaves endoglin. Sequence analysis revealed a conserved peptide in endoglin similar to the α-thrombin cleavage site of protease-activated receptor-1. Western blot analysis of plasma from preeclamptic women showed endoglin fragments consistent with thrombin-mediated cleavage. Incubation of purified endoglin with thrombin generated specific fragments, whose N- and C-terminal sequencing confirmed the predicted cleavage sites. Furthermore, thrombin treatment of endoglin-expressing cells released sEng and reduced cell surface endoglin. These findings suggest that multiple protease-targeted cleavage sites lead to the generation of sEng fragments, which may reflect endothelial dysfunction and preeclampsia progression.
Authors
- David M. Smadja (ORCID: https://orcid.org/0000-0001-7731-9202)
- Cécile V. Denis (ORCID: https://orcid.org/0000-0001-5152-9156)
- Carmelo Bernabéu (ORCID: https://orcid.org/0000-0002-1563-6162)
- Divina El Hamaoui (ORCID: https://orcid.org/0000-0003-1384-1207)
- Franck Lebrin (ORCID: https://orcid.org/0000-0002-1650-6757)
- Etienne Reboul (ORCID: https://orcid.org/0000-0003-0759-4756)
- Samuela Pasquali (ORCID: https://orcid.org/0000-0003-1487-0894)
- Pascale Gaussem (ORCID: https://orcid.org/0000-0002-9139-2147)
- Alexandre Kauskot (ORCID: https://orcid.org/0000-0002-4064-8114)
- Elisa Rossi (ORCID: https://orcid.org/0000-0002-0570-6104)
- Sophie Gandrille (ORCID: https://orcid.org/0000-0003-1367-6352)
- Aurore Marchelli (ORCID: https://orcid.org/0000-0002-8638-306X)
- Luca Jovine (ORCID: https://orcid.org/0000-0002-2679-6946)
- Alain Stépanian (ORCID: https://orcid.org/0000-0002-2942-0901)
- Bruno Palmier
Institutions
- Centre National de la Recherche Scientifique (FR)
- Consejo Superior de Investigaciones Científicas (ES)
- Inserm (FR)
- Université Paris Cité (FR)
- Université Paris-Saclay (FR)
- Leiden University Medical Center (NL)
- Karolinska Institutet (SE)
- Sorbonne Paris Cité (FR)
- Assistance Publique – Hôpitaux de Paris (FR)
- Hôpital Européen Georges-Pompidou (FR)
- Hôpital Européen (FR)
- Hôpital Saint Eloi (FR)
- Centro de Investigaciones Biológicas Margarita Salas (ES)
- ESPCI Paris (FR)
Publication Details
- Journal
- Communications Biology
- Published
- 2025-02-26
- DOI
- https://doi.org/10.1038/s42003-025-07751-3
- Citations
- 6
- Primary Topic
- Pregnancy and preeclampsia studies
- Type
- article
- Field-Weighted Citation Impact
- 12.34