Augmented Placental Protein 13 in Placental-Associated Extracellular Vesicles in Term and Preterm Preeclampsia Is Further Elevated by Corticosteroids
Placental protein 13 (PP13) is a regulatory protein involved in remodeling the vascular system of the pregnancy and extending the immune tolerance of the mother to the growing fetus. PP13 is localized on the surface of the syncytiotrophoblast. An ex vivo placental model shows that the PP13 is releas...
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MDPI AG
2023-07-01
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| author | Marina Marks Kazatsker Adi Sharabi-Nov Hamutal Meiri Rami Sammour Marei Sammar |
| author_facet | Marina Marks Kazatsker Adi Sharabi-Nov Hamutal Meiri Rami Sammour Marei Sammar |
| author_sort | Marina Marks Kazatsker |
| collection | DOAJ |
| description | Placental protein 13 (PP13) is a regulatory protein involved in remodeling the vascular system of the pregnancy and extending the immune tolerance of the mother to the growing fetus. PP13 is localized on the surface of the syncytiotrophoblast. An ex vivo placental model shows that the PP13 is released via placental-associated extracellular vesicles (PEVs) to the maternal uterine vein. This exploratory study aimed to determine PEV-associated PP13 in the maternal circulation as compared to the known soluble fraction since each has a specific communication pathway. Patients admitted to Bnai Zion Medical Center for delivery were recruited, and included 19 preeclampsia (PE) patients (7 preterm PE gestational age < 37 weeks’ gestation), 16 preterm delivery (PTD, delivery at GA < 37 weeks’ gestation), and 15 matched term delivery controls. Treatment by corticosteroids (Celestone), which is often given to patients with suspected preterm PE and PTD, was recorded. The PEV proteome was purified from the patients’ plasma by size exclusion chromatography (SEC) to separate the soluble and PEV-associated PP13. The total level of PP13 (soluble and PEV-associated) was determined using mild detergent that depleted the PEV proteome. PP13 fractions were determined by ELISA with PP13 specific antibodies. ELISA with alkaline phosphatase (PLAP)- and cluster differentiation 63 (CD63)-specific antibodies served to verify the placental origin of the PEVs. SPSS was used for statistical analysis. The patients’ medical, pregnancy, and delivery records in all groups were similar except, as expected, that a larger number of PE and PTD patients had smaller babies who were delivered earlier, and the PE patients had hypertension and proteinuria. The SEC analysis detected the presence of PP13 in the cargo of the PEVs and on their surface, in addition to the known soluble fraction. The median soluble PP13 was not significantly different across the PE, PTD, and term delivery control groups. However, after depleting the PEV of their proteome, the total PP13 (soluble and PEV-associated) was augmented in the cases of preterm PE, reaching 2153 pg/mL [IQR 1866–2838] but not in cases of PTD reaching 1576 pg/mL [1011–2014] or term delivery groups reaching 964 pg/mL [875–1636]), <i>p</i> < 0.01. On the surface of the circulating PEV from PTD patients, there was a decrease in PP13. Corticosteroid treatment was accompanied by a massive depletion of PP13 from the PEV, especially in preterm PE patients. This exploratory study is, thus, the first to determine PEV-associated PP13 in maternal circulation, providing a quantitative determination of the soluble and the PEV-associated fractions, and it shows that the latter is the larger. We found an increase in the amount of PP13 carried via the PEV-associated pathway in PE and PTD patients compared to term delivery cases, which was further augmented when the patients were treated with corticosteroids, especially in preterm PE. The signal conveyed by this novel communication pathway warrants further research to investigate these two differential pathways for the liberation of PP13. |
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| spelling | doaj.art-14364bc604c742c6a5720704cc7a38f12023-11-18T22:59:39ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-07-0124151205110.3390/ijms241512051Augmented Placental Protein 13 in Placental-Associated Extracellular Vesicles in Term and Preterm Preeclampsia Is Further Elevated by CorticosteroidsMarina Marks Kazatsker0Adi Sharabi-Nov1Hamutal Meiri2Rami Sammour3Marei Sammar4Maternal and Fetal Medicine Unit, Department of Obstetrics and Gynecology, Bnai-Zion University Medical Center, Haifa 3498838, IsraelDepartment of Statistics, Tel Hai Academic College, Tel Hai 122103, IsraelHy-Laboratories Ltd., Rehovot 7670606, IsraelMaternal and Fetal Medicine Unit, Department of Obstetrics and Gynecology, Bnai-Zion University Medical Center, Haifa 3498838, IsraelProf. Ephraim Katzir Department of Biotechnology Engineering, Braude Academic College of Engineering, 51 Snunit St., Karmiel 2161002, IsraelPlacental protein 13 (PP13) is a regulatory protein involved in remodeling the vascular system of the pregnancy and extending the immune tolerance of the mother to the growing fetus. PP13 is localized on the surface of the syncytiotrophoblast. An ex vivo placental model shows that the PP13 is released via placental-associated extracellular vesicles (PEVs) to the maternal uterine vein. This exploratory study aimed to determine PEV-associated PP13 in the maternal circulation as compared to the known soluble fraction since each has a specific communication pathway. Patients admitted to Bnai Zion Medical Center for delivery were recruited, and included 19 preeclampsia (PE) patients (7 preterm PE gestational age < 37 weeks’ gestation), 16 preterm delivery (PTD, delivery at GA < 37 weeks’ gestation), and 15 matched term delivery controls. Treatment by corticosteroids (Celestone), which is often given to patients with suspected preterm PE and PTD, was recorded. The PEV proteome was purified from the patients’ plasma by size exclusion chromatography (SEC) to separate the soluble and PEV-associated PP13. The total level of PP13 (soluble and PEV-associated) was determined using mild detergent that depleted the PEV proteome. PP13 fractions were determined by ELISA with PP13 specific antibodies. ELISA with alkaline phosphatase (PLAP)- and cluster differentiation 63 (CD63)-specific antibodies served to verify the placental origin of the PEVs. SPSS was used for statistical analysis. The patients’ medical, pregnancy, and delivery records in all groups were similar except, as expected, that a larger number of PE and PTD patients had smaller babies who were delivered earlier, and the PE patients had hypertension and proteinuria. The SEC analysis detected the presence of PP13 in the cargo of the PEVs and on their surface, in addition to the known soluble fraction. The median soluble PP13 was not significantly different across the PE, PTD, and term delivery control groups. However, after depleting the PEV of their proteome, the total PP13 (soluble and PEV-associated) was augmented in the cases of preterm PE, reaching 2153 pg/mL [IQR 1866–2838] but not in cases of PTD reaching 1576 pg/mL [1011–2014] or term delivery groups reaching 964 pg/mL [875–1636]), <i>p</i> < 0.01. On the surface of the circulating PEV from PTD patients, there was a decrease in PP13. Corticosteroid treatment was accompanied by a massive depletion of PP13 from the PEV, especially in preterm PE patients. This exploratory study is, thus, the first to determine PEV-associated PP13 in maternal circulation, providing a quantitative determination of the soluble and the PEV-associated fractions, and it shows that the latter is the larger. We found an increase in the amount of PP13 carried via the PEV-associated pathway in PE and PTD patients compared to term delivery cases, which was further augmented when the patients were treated with corticosteroids, especially in preterm PE. The signal conveyed by this novel communication pathway warrants further research to investigate these two differential pathways for the liberation of PP13.https://www.mdpi.com/1422-0067/24/15/12051extracellular vesiclesplacental protein 13 (PP13)galectin 13preeclampsia (PE)preterm delivery (PTD)size exclusion chromatography (SEC) |
| spellingShingle | Marina Marks Kazatsker Adi Sharabi-Nov Hamutal Meiri Rami Sammour Marei Sammar Augmented Placental Protein 13 in Placental-Associated Extracellular Vesicles in Term and Preterm Preeclampsia Is Further Elevated by Corticosteroids International Journal of Molecular Sciences extracellular vesicles placental protein 13 (PP13) galectin 13 preeclampsia (PE) preterm delivery (PTD) size exclusion chromatography (SEC) |
| title | Augmented Placental Protein 13 in Placental-Associated Extracellular Vesicles in Term and Preterm Preeclampsia Is Further Elevated by Corticosteroids |
| title_full | Augmented Placental Protein 13 in Placental-Associated Extracellular Vesicles in Term and Preterm Preeclampsia Is Further Elevated by Corticosteroids |
| title_fullStr | Augmented Placental Protein 13 in Placental-Associated Extracellular Vesicles in Term and Preterm Preeclampsia Is Further Elevated by Corticosteroids |
| title_full_unstemmed | Augmented Placental Protein 13 in Placental-Associated Extracellular Vesicles in Term and Preterm Preeclampsia Is Further Elevated by Corticosteroids |
| title_short | Augmented Placental Protein 13 in Placental-Associated Extracellular Vesicles in Term and Preterm Preeclampsia Is Further Elevated by Corticosteroids |
| title_sort | augmented placental protein 13 in placental associated extracellular vesicles in term and preterm preeclampsia is further elevated by corticosteroids |
| topic | extracellular vesicles placental protein 13 (PP13) galectin 13 preeclampsia (PE) preterm delivery (PTD) size exclusion chromatography (SEC) |
| url | https://www.mdpi.com/1422-0067/24/15/12051 |
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