Thrombin cleaves membrane-bound endoglin potentially contributing to the heterogeneity of circulating endoglin in preeclampsia
Abstract 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....
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Nature Portfolio
2025-02-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-025-07751-3 |
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| author | Divina El Hamaoui Aurore Marchelli Sophie Gandrille Etienne Reboul Alain Stepanian Bruno Palmier Luca Jovine Franck Lebrin David M. Smadja Carmelo Bernabeu Cecile V. Denis Pascale Gaussem Samuela Pasquali Alexandre Kauskot Elisa Rossi |
| author_facet | Divina El Hamaoui Aurore Marchelli Sophie Gandrille Etienne Reboul Alain Stepanian Bruno Palmier Luca Jovine Franck Lebrin David M. Smadja Carmelo Bernabeu Cecile V. Denis Pascale Gaussem Samuela Pasquali Alexandre Kauskot Elisa Rossi |
| author_sort | Divina El Hamaoui |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-1cbb7d4d40fe4d78ba3fc1abc02cb0e5 |
| institution | DOAJ |
| issn | 2399-3642 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-1cbb7d4d40fe4d78ba3fc1abc02cb0e52025-08-20T02:59:37ZengNature PortfolioCommunications Biology2399-36422025-02-018111210.1038/s42003-025-07751-3Thrombin cleaves membrane-bound endoglin potentially contributing to the heterogeneity of circulating endoglin in preeclampsiaDivina El Hamaoui0Aurore Marchelli1Sophie Gandrille2Etienne Reboul3Alain Stepanian4Bruno Palmier5Luca Jovine6Franck Lebrin7David M. Smadja8Carmelo Bernabeu9Cecile V. Denis10Pascale Gaussem11Samuela Pasquali12Alexandre Kauskot13Elisa Rossi14Innovative Therapies in Hemostasis, INSERM U1140, Université Paris CitéInnovative Therapies in Hemostasis, INSERM U1140, Université Paris CitéInnovative Therapies in Hemostasis, INSERM U1140, Université Paris CitéInnovative Therapies in Hemostasis, INSERM U1140, Université Paris CitéService d’Hématologie biologiqueInnovative Therapies in Hemostasis, INSERM U1140, Université Paris CitéKarolinska Institutet, Department of Medicine (MedH)Einthoven Laboratory for Experimental Vascular Medicine, Department of Internal Medicine (Nephrology), Leiden University Medical CenterInnovative Therapies in Hemostasis, INSERM U1140, Université Paris CitéCentro de Investigaciones Biológicas Margarita Salas, Consejo Superior de Investigaciones Científicas (CSIC)HITh, Unite Mixte de Recherche 1176 INSERM, Université Paris-SaclayInnovative Therapies in Hemostasis, INSERM U1140, Université Paris CitéLaboratoire Biologie Fonctionnelle et Adaptative, INSERM ERL1133 F-75013HITh, Unite Mixte de Recherche 1176 INSERM, Université Paris-SaclayInnovative Therapies in Hemostasis, INSERM U1140, Université Paris CitéAbstract 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.https://doi.org/10.1038/s42003-025-07751-3 |
| spellingShingle | Divina El Hamaoui Aurore Marchelli Sophie Gandrille Etienne Reboul Alain Stepanian Bruno Palmier Luca Jovine Franck Lebrin David M. Smadja Carmelo Bernabeu Cecile V. Denis Pascale Gaussem Samuela Pasquali Alexandre Kauskot Elisa Rossi Thrombin cleaves membrane-bound endoglin potentially contributing to the heterogeneity of circulating endoglin in preeclampsia Communications Biology |
| title | Thrombin cleaves membrane-bound endoglin potentially contributing to the heterogeneity of circulating endoglin in preeclampsia |
| title_full | Thrombin cleaves membrane-bound endoglin potentially contributing to the heterogeneity of circulating endoglin in preeclampsia |
| title_fullStr | Thrombin cleaves membrane-bound endoglin potentially contributing to the heterogeneity of circulating endoglin in preeclampsia |
| title_full_unstemmed | Thrombin cleaves membrane-bound endoglin potentially contributing to the heterogeneity of circulating endoglin in preeclampsia |
| title_short | Thrombin cleaves membrane-bound endoglin potentially contributing to the heterogeneity of circulating endoglin in preeclampsia |
| title_sort | thrombin cleaves membrane bound endoglin potentially contributing to the heterogeneity of circulating endoglin in preeclampsia |
| url | https://doi.org/10.1038/s42003-025-07751-3 |
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