Ginsenoside Rg3 promotes the survival and migration of trophoblast cells in a rat model of gestational hypertension by regulating mir-100a/insulin growth factor-2 axis

Abstract

Objective: Preeclampsia (PE) is a common complication during pregnancy. miR-100a is expressed in the placenta and regulates the survival and development of placental cells. Insulin growth factor-2 (IGF-2) may serve as its downstream target. This study investigated the protective mechanisms of ginsenoside Rg3 against PE in rat model. Materials and Methods: LPS-induced rat PE models were suitable for intravenous administration of the highly expressed miR-100a ginsenoside Rg3 lentiviral vector. Human trophoblasts were cultured in vitro for JEG-3, and PE cell models were constructed. In vivo effects on tumor growth and apoptosis were observed. Ginsenoside Rg3 was treated with different concentrations of shRNA, miR-100a analogs, inhibitors, or IGF-2. Autophagy and the expression of autophagy-related proteins were examined. Trophoblast activity and migration were determined using Cell Counting Kit-8 and Transwell assays. Both drugs strongly inhibited trophoblasts under normal conditions with some synergy between them. Double-luciferase return assay confirmed the binding affinity of miR-100a for IGF-2. Results: In response to Rg3, autophagy and the expression of autophagy-related proteins LC3-I/II, Beclin1, and SQSTM1 were reduced in PE rat placental trophoblasts. Rg3 inhibited autophagy in JEG-3 cells and promoted JEG-3 survival and migration in a concentration-dependent manner. miR-100a upregulated PE expression. These results suggested that autophagy was a vital signaling system. Rg3 intervention inhibited miR-100a expression and miR-100a downregulated IGF-2 expression in placental tissues and promoted autophagy, thereby inhibiting JEG-3 cell survival and migration. In rats, Rg3 inhibited PE development by regulating the activity of the miR-100a-IGF-2 signaling axis. Conclusion: Ginsenoside Rg3 positively regulates the miR-100a-IGF-2 axis and protects PE rats by inhibiting trophoblastic autophagy and promoting trophoblastic cell survival and migration.

Keywords

• ginsenoside rg3
• inflammatory response
• mir-100a/insulin growth factor-2 axis
• preeclampsia
• pregnancy-induced hypertension