Proteomic studies of VEGFR2 in human placentas reveal protein associations with preeclampsia, diabetes, gravidity, and labor
Abstract VEGFR2 (Vascular endothelial growth factor receptor 2) is a central regulator of placental angiogenesis. The study of the VEGFR2 proteome of chorionic villi at term revealed its partners MDMX (Double minute 4 protein) and PICALM (Phosphatidylinositol-binding clathrin assembly protein). Subs...
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| Format: | Article |
| Language: | English |
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BMC
2024-04-01
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| Series: | Cell Communication and Signaling |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12964-024-01567-0 |
| _version_ | 1797209202213519360 |
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| author | Shannon J. Ho Dale Chaput Rachel G. Sinkey Amanda H. Garces Erika P. New Maja Okuka Peng Sang Sefa Arlier Nihan Semerci Thora S. Steffensen Thomas J. Rutherford Angel E. Alsina Jianfeng Cai Matthew L. Anderson Ronald R. Magness Vladimir N. Uversky Derek A. T. Cummings John C. M. Tsibris |
| author_facet | Shannon J. Ho Dale Chaput Rachel G. Sinkey Amanda H. Garces Erika P. New Maja Okuka Peng Sang Sefa Arlier Nihan Semerci Thora S. Steffensen Thomas J. Rutherford Angel E. Alsina Jianfeng Cai Matthew L. Anderson Ronald R. Magness Vladimir N. Uversky Derek A. T. Cummings John C. M. Tsibris |
| author_sort | Shannon J. Ho |
| collection | DOAJ |
| description | Abstract VEGFR2 (Vascular endothelial growth factor receptor 2) is a central regulator of placental angiogenesis. The study of the VEGFR2 proteome of chorionic villi at term revealed its partners MDMX (Double minute 4 protein) and PICALM (Phosphatidylinositol-binding clathrin assembly protein). Subsequently, the oxytocin receptor (OT-R) and vasopressin V1aR receptor were detected in MDMX and PICALM immunoprecipitations. Immunogold electron microscopy showed VEGFR2 on endothelial cell (EC) nuclei, mitochondria, and Hofbauer cells (HC), tissue-resident macrophages of the placenta. MDMX, PICALM, and V1aR were located on EC plasma membranes, nuclei, and HC nuclei. Unexpectedly, PICALM and OT-R were detected on EC projections into the fetal lumen and OT-R on 20–150 nm clusters therein, prompting the hypothesis that placental exosomes transport OT-R to the fetus and across the blood–brain barrier. Insights on gestational complications were gained by univariable and multivariable regression analyses associating preeclampsia with lower MDMX protein levels in membrane extracts of chorionic villi, and lower MDMX, PICALM, OT-R, and V1aR with spontaneous vaginal deliveries compared to cesarean deliveries before the onset of labor. We found select associations between higher MDMX, PICALM, OT-R protein levels and either gravidity, diabetes, BMI, maternal age, or neonatal weight, and correlations only between PICALM-OT-R (p < 2.7 × 10–8), PICALM-V1aR (p < 0.006), and OT-R-V1aR (p < 0.001). These results offer for exploration new partnerships in metabolic networks, tissue-resident immunity, and labor, notably for HC that predominantly express MDMX. |
| first_indexed | 2024-04-24T09:50:57Z |
| format | Article |
| id | doaj.art-4a1dc85d29c94f1b8404ba416c726589 |
| institution | Directory Open Access Journal |
| issn | 1478-811X |
| language | English |
| last_indexed | 2024-04-24T09:50:57Z |
| publishDate | 2024-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell Communication and Signaling |
| spelling | doaj.art-4a1dc85d29c94f1b8404ba416c7265892024-04-14T11:23:16ZengBMCCell Communication and Signaling1478-811X2024-04-0122112310.1186/s12964-024-01567-0Proteomic studies of VEGFR2 in human placentas reveal protein associations with preeclampsia, diabetes, gravidity, and laborShannon J. Ho0Dale Chaput1Rachel G. Sinkey2Amanda H. Garces3Erika P. New4Maja Okuka5Peng Sang6Sefa Arlier7Nihan Semerci8Thora S. Steffensen9Thomas J. Rutherford10Angel E. Alsina11Jianfeng Cai12Matthew L. Anderson13Ronald R. Magness14Vladimir N. Uversky15Derek A. T. Cummings16John C. M. Tsibris17Department of Obstetrics and Gynecology, University of South FloridaDepartment of Cell Biology, Microbiology and Molecular Biology, University of South FloridaDepartment of Obstetrics and Gynecology, University of South FloridaLisa Muma Weitz Microscopy Laboratory, University of South FloridaDepartment of Obstetrics and Gynecology, University of South FloridaDepartment of Obstetrics and Gynecology, University of South FloridaDepartment of Chemistry, University of South FloridaDepartment of Obstetrics and Gynecology, University of South FloridaDepartment of Obstetrics and Gynecology, University of South FloridaDepartment of Pathology, Tampa General HospitalDepartment of Obstetrics and Gynecology, University of South FloridaTransplant Surgery Center, Tampa General HospitalDepartment of Chemistry, University of South FloridaDepartment of Obstetrics and Gynecology, University of South FloridaDepartment of Obstetrics and Gynecology, University of South FloridaDepartment of Molecular Medicine, University of South FloridaDepartment of Biology and Emerging Pathogens Institute, University of FloridaDepartment of Obstetrics and Gynecology, University of South FloridaAbstract VEGFR2 (Vascular endothelial growth factor receptor 2) is a central regulator of placental angiogenesis. The study of the VEGFR2 proteome of chorionic villi at term revealed its partners MDMX (Double minute 4 protein) and PICALM (Phosphatidylinositol-binding clathrin assembly protein). Subsequently, the oxytocin receptor (OT-R) and vasopressin V1aR receptor were detected in MDMX and PICALM immunoprecipitations. Immunogold electron microscopy showed VEGFR2 on endothelial cell (EC) nuclei, mitochondria, and Hofbauer cells (HC), tissue-resident macrophages of the placenta. MDMX, PICALM, and V1aR were located on EC plasma membranes, nuclei, and HC nuclei. Unexpectedly, PICALM and OT-R were detected on EC projections into the fetal lumen and OT-R on 20–150 nm clusters therein, prompting the hypothesis that placental exosomes transport OT-R to the fetus and across the blood–brain barrier. Insights on gestational complications were gained by univariable and multivariable regression analyses associating preeclampsia with lower MDMX protein levels in membrane extracts of chorionic villi, and lower MDMX, PICALM, OT-R, and V1aR with spontaneous vaginal deliveries compared to cesarean deliveries before the onset of labor. We found select associations between higher MDMX, PICALM, OT-R protein levels and either gravidity, diabetes, BMI, maternal age, or neonatal weight, and correlations only between PICALM-OT-R (p < 2.7 × 10–8), PICALM-V1aR (p < 0.006), and OT-R-V1aR (p < 0.001). These results offer for exploration new partnerships in metabolic networks, tissue-resident immunity, and labor, notably for HC that predominantly express MDMX.https://doi.org/10.1186/s12964-024-01567-0VEGFR2MDMXPICALMOxytocin receptorVasopressin receptor V1aRHofbauer cells |
| spellingShingle | Shannon J. Ho Dale Chaput Rachel G. Sinkey Amanda H. Garces Erika P. New Maja Okuka Peng Sang Sefa Arlier Nihan Semerci Thora S. Steffensen Thomas J. Rutherford Angel E. Alsina Jianfeng Cai Matthew L. Anderson Ronald R. Magness Vladimir N. Uversky Derek A. T. Cummings John C. M. Tsibris Proteomic studies of VEGFR2 in human placentas reveal protein associations with preeclampsia, diabetes, gravidity, and labor Cell Communication and Signaling VEGFR2 MDMX PICALM Oxytocin receptor Vasopressin receptor V1aR Hofbauer cells |
| title | Proteomic studies of VEGFR2 in human placentas reveal protein associations with preeclampsia, diabetes, gravidity, and labor |
| title_full | Proteomic studies of VEGFR2 in human placentas reveal protein associations with preeclampsia, diabetes, gravidity, and labor |
| title_fullStr | Proteomic studies of VEGFR2 in human placentas reveal protein associations with preeclampsia, diabetes, gravidity, and labor |
| title_full_unstemmed | Proteomic studies of VEGFR2 in human placentas reveal protein associations with preeclampsia, diabetes, gravidity, and labor |
| title_short | Proteomic studies of VEGFR2 in human placentas reveal protein associations with preeclampsia, diabetes, gravidity, and labor |
| title_sort | proteomic studies of vegfr2 in human placentas reveal protein associations with preeclampsia diabetes gravidity and labor |
| topic | VEGFR2 MDMX PICALM Oxytocin receptor Vasopressin receptor V1aR Hofbauer cells |
| url | https://doi.org/10.1186/s12964-024-01567-0 |
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