Abstract P227: Gq Signaling In The Placental Syncytiotrophoblast Layer During Preeclampsia
| Autor: | Justin L. Grobe, Mary Christine Livergood, Curt D. Sigmund, Jennifer McIntosh, Megan Opichka |
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| Rok vydání: | 2021 |
| Předmět: | |
| Zdroj: | Hypertension. 78 |
| ISSN: | 1524-4563 0194-911X |
| DOI: | 10.1161/hyp.78.suppl_1.p227 |
| Popis: | Hormones implicated in preeclampsia (PE) such as angiotensin, endothelin, and vasopressin signal via receptors coupled to the Gq cascade, and Regulator of G protein Signaling-2 (RGS2) buffers this signaling. We have published that RGS2 expression is decreased in human PE placenta, and reducing RGS2 in placenta causes development of key features of PE in mice. New in situ hybridization data indicate that in both humans and mice, RGS2 is abundant among many cell types in the placenta, including the syncytiotrophoblast (STB) layer. In addition, RGS2 expression in the human STB layer is reduced during PE. As this layer is strongly implicated in PE, these data lead us to hypothesize a critical Gq-buffering role for RGS2 in STB cells to prevent PE. To explore the effect of excess Gq signaling within the STB layer, we utilized a Cre-Lox approach to cause expression of the Gq-coupled hM3Dq DREADD throughout the fetoplacental unit (dam: hM3Dq+, sire: Actb-Cre+) or only within the STB layer (dam: hM3Dq+, sire: Gcm1-Cre+), and then activated the hM3Dq receptor via clozapine N-oxide (CNO, 0.5 to 2 mg/kg) injection in mid-gestation (GD12.5-14.5) before tissue collection at GD14.5. Gαq activation throughout the fetoplacental unit (Actb-Cre model) severely restricted fetoplacental growth compared to saline-injected controls (n=2 vs 3; placenta: 0.027±0.006 vs 0.115±0.021 g; p |
| Databáze: | OpenAIRE |
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