2. Academic Validation
  3. The Effect of FPR2 on the Regulation of Trophoblast Autophagy via the PI3K/AKT/mTOR Signaling Pathway in Preeclampsia

The Effect of FPR2 on the Regulation of Trophoblast Autophagy via the PI3K/AKT/mTOR Signaling Pathway in Preeclampsia

  • FASEB J. 2025 Jun 15;39(11):e70697. doi: 10.1096/fj.202402938RR.
Ning Jiang 1,  Meijuan Zhou 2,  Yingying Le 3,  Li Xiao 2,  Changqing Zhang 2,  Shuxian Li 2,  Junjun Guo 2,  Yue Wu 4,  Meihua Zhang 2,  Xietong Wang 1 2
Affiliations

Affiliations

  • 1 Department of Obstetrics and Gynecology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.
  • 2 Key Laboratory of Maternal & Fetal Medicine of National Health Commission of China, Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan, China.
  • 3 CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, Shanghai, China.
  • 4 Department of Clinic, The Second Affiliated Hospital of Shandong University of Chinese Medicine, Jinan, China.
PMID: 40474580 DOI: 10.1096/fj.202402938RR
Abstract

Preeclampsia (PE) is associated with significant maternal and fetal morbidity and mortality, with placental trophoblast dysfunction playing a central role in its pathogenesis. Autophagic imbalance impacts trophoblast function, and the regulatory role of formyl-peptide receptor 2 (FPR2) in trophoblast Autophagy and placental function requires further investigation. We used the HTR8/SVneo cell line and Fpr2 knockout mice to explore the role of FPR2 in trophoblast function. The expression of FPR2 and Autophagy levels were elevated in PE patients and models. FPR2 knockdown reversed the H2O2-induced inhibition of trophoblast function and downregulated autophagy-related proteins. H2O2 activated the PI3K/Akt/mTOR pathway, but this activation was reduced by FPR2 knockdown or 3-MA pretreatment. We demonstrate that FPR2 regulates trophoblast Autophagy through the PI3K/Akt/mTOR signaling pathway, contributing to the development of PE. These findings may offer new insights into the prevention and treatment of PE.

Keywords

FPR2; HTR8/SVneo cells; PI3K/AKT/mTOR; autophagy; preeclampsia (PE).

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