Ras p21 protein activator 1 regulates trophoblast function and its association with preeclampsia through the Ras/mitogen-activated protein kinase pathway.

OBJECTIVE: Ras p21 protein activator 1 (RASA1) plays a crucial role in the placenta. However, its effects and mechanisms of RASA1 on trophoblast function in preeclampsia (PE) are unclear. This study aims to investigate the relationship between the regulation of the Ras/mitogen-activated protein kinase (MAPK) pathway by RASA1 and the function of trophoblast cells in PE. MATERIAL AND METHODS: Placental tissues were collected from patients with early-onset PE and late-onset PE and their gestational age-matched normal pregnancies. Western blot analysis and quantitative reverse transcription polymerase chain reaction were employed to assess RASA1 levels in placental tissues and trophoblast cells, as well as Ras activation and p38 MAPK phosphorylation levels in the Ras/MAPK pathway. Wound healing, cell counting kit-8, and Transwell migration and invasion assays and flow cytometry experiments were conducted to detect the proliferation, migration, invasion, and apoptosis capabilities of trophoblast cells. RESULTS: RASA1 was significantly overexpressed in the placental tissues of patients with PE (P < 0.05). In cells, it downregulated the activation of Ras and phosphorylation of p38 MAPK (P < 0.05) and reduced proliferation and inhibited migration and invasive capabilities (P < 0.05). Moreover, RASA1 increased the rate of apoptosis, promoted the protein expression levels of cleaved caspase3 and Bax, and inhibited the expression of Bcl2 in cells (P < 0.05). The P38/MAPK inhibitor SB203580 reversed the activation of the Ras/MAPK pathway and the effects on proliferation, migration, invasion, and apoptosis of cells induced by si-RASA1 (P < 0.05). CONCLUSION: The activity of the Ras/MAPK pathway could be inhibited by high RASA1 expression, which suppresses cell invasion, migration, and proliferation and boosts apoptosis. The abnormal regulation of the RASA1-Ras/MAPK axis may be a key factor in the development of PE and, therefore, provides new ideas and clinically effective strategies for the diagnosis and treatment of this condition.