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Background <p>Early-onset preeclampsia (EOPE) is a serious condition characterized by dysregulated trophoblast Invasiveness, leading to inadequate reconstruction of uterine spiral arteries and shallow placental implantation. ELA is a recently discovered protein which serves as an endogenous ligand of the angiotensin receptor AT1-related receptor protein(APJ). It has been found to have high cross species conservation and high expression in the placenta, indicating that it may play an important physiological role in pregnancy. This study aimed to evaluate the role of ELA in the context of EOPE and its impact on trophoblast function.</p> Methods <p>Placental tissue samples from normal pregnancies, preterm births, and EOPE cases were analyzed for ELA expression in cytotrophoblasts and syncytiotrophoblasts. Levels of ELA and APJ were measured and compared among the different groups. Additionally, HTR-8/SVneo cells were utilized to assess the functional effects of ELA silencing and overexpression on cell migration and invasion. The involvement of the METTL3/PI3K/AKT signaling pathway was also investigated through the knockdown of METTL3.</p> Results <p>While the mRNA and protein levels of ELA and APJ showed no significant changes between normal pregnancies and preterm births, significantly lower ELA and APJ levels were observed in samples from the EOPE group compared to those from normal pregnancies. Silencing ELA in HTR-8/SVneo cells led to compromised migratory and invasive potential, accompanied by decreased levels of key kinases associated with the METTL3/PI3K/AKT pathway. Conversely, ELA overexpression resulted in enhanced migration and invasion. Additionally, knockdown of METTL3 inhibited cell migration and invasion, correlating with reduced kinase levels within the same signaling pathway.</p> Conclusion <p>Our findings indicate that ELA plays a crucial role in stimulating trophoblastic cell migratory and invasive activities through the activation of METTL3/PI3K/AKT signaling. This suggests that dysregulation of ELA could contribute to the pathogenesis of EOPE. The results highlight potential avenues for developing novel therapeutic strategies for this serious condition.</p> Clinical trial number <p>Not applicable.</p>

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ELABELA targets the METTL3/PI3K/AKT axis to enhance trophoblast invasion in early-onset preeclampsia

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月10日

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  • Lijing Wang,
  • Xiaokun Wang,
  • Xue Wang,
  • Mingsheng Wu,
  • Minghui Ou,
  • Ningning He

摘要

Background

Early-onset preeclampsia (EOPE) is a serious condition characterized by dysregulated trophoblast Invasiveness, leading to inadequate reconstruction of uterine spiral arteries and shallow placental implantation. ELA is a recently discovered protein which serves as an endogenous ligand of the angiotensin receptor AT1-related receptor protein(APJ). It has been found to have high cross species conservation and high expression in the placenta, indicating that it may play an important physiological role in pregnancy. This study aimed to evaluate the role of ELA in the context of EOPE and its impact on trophoblast function.

Methods

Placental tissue samples from normal pregnancies, preterm births, and EOPE cases were analyzed for ELA expression in cytotrophoblasts and syncytiotrophoblasts. Levels of ELA and APJ were measured and compared among the different groups. Additionally, HTR-8/SVneo cells were utilized to assess the functional effects of ELA silencing and overexpression on cell migration and invasion. The involvement of the METTL3/PI3K/AKT signaling pathway was also investigated through the knockdown of METTL3.

Results

While the mRNA and protein levels of ELA and APJ showed no significant changes between normal pregnancies and preterm births, significantly lower ELA and APJ levels were observed in samples from the EOPE group compared to those from normal pregnancies. Silencing ELA in HTR-8/SVneo cells led to compromised migratory and invasive potential, accompanied by decreased levels of key kinases associated with the METTL3/PI3K/AKT pathway. Conversely, ELA overexpression resulted in enhanced migration and invasion. Additionally, knockdown of METTL3 inhibited cell migration and invasion, correlating with reduced kinase levels within the same signaling pathway.

Conclusion

Our findings indicate that ELA plays a crucial role in stimulating trophoblastic cell migratory and invasive activities through the activation of METTL3/PI3K/AKT signaling. This suggests that dysregulation of ELA could contribute to the pathogenesis of EOPE. The results highlight potential avenues for developing novel therapeutic strategies for this serious condition.

Clinical trial number

Not applicable.