PPAR-γ Regulates Trophoblast Differentiation in the BeWo Cell Model
Common pregnancy complications, such as severe preeclampsia and intrauterine growth restriction, disrupt pregnancy progression and impair maternal and fetal wellbeing. Placentas from such pregnancies exhibit lesions principally within the syncytiotrophoblast (SCT), a layer in direct contact with mat...
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| Format: | Article |
| Language: | English |
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Wiley
2014-01-01
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| Series: | PPAR Research |
| Online Access: | http://dx.doi.org/10.1155/2014/637251 |
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| author | Khrystyna Levytska Sascha Drewlo Dora Baczyk John Kingdom |
| author_facet | Khrystyna Levytska Sascha Drewlo Dora Baczyk John Kingdom |
| author_sort | Khrystyna Levytska |
| collection | DOAJ |
| description | Common pregnancy complications, such as severe preeclampsia and intrauterine growth restriction, disrupt pregnancy progression and impair maternal and fetal wellbeing. Placentas from such pregnancies exhibit lesions principally within the syncytiotrophoblast (SCT), a layer in direct contact with maternal blood. In humans and mice, glial cell missing-1 (GCM-1) promotes differentiation of underlying cytotrophoblast cells into the outer SCT layer. GCM-1 may be regulated by the transcription factor peroxisome proliferator-activated receptor-gamma (PPAR-γ); in mice, PPAR-γ promotes labyrinthine trophoblast differentiation via Gcm-1, and, as we previously demonstrated, PPAR-γ activation ameliorates disease features in rat model of preeclampsia. Here, we aimed to characterize the baseline activity of PPAR-γ in the human choriocarcinoma BeWo cell line that mimics SCT formation in vitro and modulate PPAR-γ activity to study its effects on cell proliferation versus differentiation. We report a novel negative autoregulatory mechanism between PPAR-γ activity and expression and show that blocking PPAR-γ activity induces cell proliferation at the expense of differentiation, while these remain unaltered following treatment with the agonist rosiglitazone. Gaining a deeper understanding of the role and activity of PPAR-γ in placental physiology will offer new avenues for the development of secondary prevention and/or treatment options for placentally-mediated pregnancy complications. |
| format | Article |
| id | doaj-art-a65e660c19584e8daa363adc9e588a4f |
| institution | Kabale University |
| issn | 1687-4757 1687-4765 |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | PPAR Research |
| spelling | doaj-art-a65e660c19584e8daa363adc9e588a4f2025-02-03T06:14:16ZengWileyPPAR Research1687-47571687-47652014-01-01201410.1155/2014/637251637251PPAR-γ Regulates Trophoblast Differentiation in the BeWo Cell ModelKhrystyna Levytska0Sascha Drewlo1Dora Baczyk2John Kingdom3Research Centre for Women’s and Infants’ Health, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Room 3-904, Toronto, ON, M5G 1Z5, CanadaDepartment of Obstetrics and Gynecology, C. S. Mott Center for Human Growth and Development, Wayne State University School of Medicine, Detroit, MI, USAResearch Centre for Women’s and Infants’ Health, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Room 3-904, Toronto, ON, M5G 1Z5, CanadaResearch Centre for Women’s and Infants’ Health, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Room 3-904, Toronto, ON, M5G 1Z5, CanadaCommon pregnancy complications, such as severe preeclampsia and intrauterine growth restriction, disrupt pregnancy progression and impair maternal and fetal wellbeing. Placentas from such pregnancies exhibit lesions principally within the syncytiotrophoblast (SCT), a layer in direct contact with maternal blood. In humans and mice, glial cell missing-1 (GCM-1) promotes differentiation of underlying cytotrophoblast cells into the outer SCT layer. GCM-1 may be regulated by the transcription factor peroxisome proliferator-activated receptor-gamma (PPAR-γ); in mice, PPAR-γ promotes labyrinthine trophoblast differentiation via Gcm-1, and, as we previously demonstrated, PPAR-γ activation ameliorates disease features in rat model of preeclampsia. Here, we aimed to characterize the baseline activity of PPAR-γ in the human choriocarcinoma BeWo cell line that mimics SCT formation in vitro and modulate PPAR-γ activity to study its effects on cell proliferation versus differentiation. We report a novel negative autoregulatory mechanism between PPAR-γ activity and expression and show that blocking PPAR-γ activity induces cell proliferation at the expense of differentiation, while these remain unaltered following treatment with the agonist rosiglitazone. Gaining a deeper understanding of the role and activity of PPAR-γ in placental physiology will offer new avenues for the development of secondary prevention and/or treatment options for placentally-mediated pregnancy complications.http://dx.doi.org/10.1155/2014/637251 |
| spellingShingle | Khrystyna Levytska Sascha Drewlo Dora Baczyk John Kingdom PPAR-γ Regulates Trophoblast Differentiation in the BeWo Cell Model PPAR Research |
| title | PPAR-γ Regulates Trophoblast Differentiation in the BeWo Cell Model |
| title_full | PPAR-γ Regulates Trophoblast Differentiation in the BeWo Cell Model |
| title_fullStr | PPAR-γ Regulates Trophoblast Differentiation in the BeWo Cell Model |
| title_full_unstemmed | PPAR-γ Regulates Trophoblast Differentiation in the BeWo Cell Model |
| title_short | PPAR-γ Regulates Trophoblast Differentiation in the BeWo Cell Model |
| title_sort | ppar γ regulates trophoblast differentiation in the bewo cell model |
| url | http://dx.doi.org/10.1155/2014/637251 |
| work_keys_str_mv | AT khrystynalevytska ppargregulatestrophoblastdifferentiationinthebewocellmodel AT saschadrewlo ppargregulatestrophoblastdifferentiationinthebewocellmodel AT dorabaczyk ppargregulatestrophoblastdifferentiationinthebewocellmodel AT johnkingdom ppargregulatestrophoblastdifferentiationinthebewocellmodel |