2. Academic Validation
  3. OLFML3 suppresses trophoblast apoptosis via the PI3K/AKT pathway: A possible therapeutic target in preeclampsia

OLFML3 suppresses trophoblast apoptosis via the PI3K/AKT pathway: A possible therapeutic target in preeclampsia

  • Placenta. 2024 Mar 6:147:1-11. doi: 10.1016/j.placenta.2024.01.008.
Haiying Chen 1,  Ruiping Li 2,  Jiangyujing Bian 3,  Xiaoqing Li 4,  Cunjing Su 3,  Yang Wang 3,  Hongping Zhang 4,  Jianqiong Zheng 4,  Yeping Wang 4,  Hong Zhang 5
Affiliations

Affiliations

  • 1 Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Soochow University, Suzhou, China.
  • 2 Department of Gastroenterology, The Second Affiliated Hospital of Soochow University, Suzhou, China.
  • 3 Pharmaceutical Research Lab, The Second Affiliated Hospital of Soochow University, Suzhou, China.
  • 4 Department of Obstetrics and Gynecology, The Third Clinical Institute Affiliated to Wenzhou Medical University, Wenzhou People's Hospital, Wenzhou Maternal and Child Health Care Hospital, Wenzhou, 325000, China.
  • 5 Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Soochow University, Suzhou, China; Jiangsu Institute of Clinical Immunology, China. Electronic address: [email protected].
PMID: 38277999 DOI: 10.1016/j.placenta.2024.01.008
Abstract

Introduction: Preeclampsia (PE) is a pregnancy complication that encompasses various pathogenic mechanisms. Shallow implantation of the placenta due to abnormal trophoblast behavior is considered an important mechanism underlying PE; however, its exact etiology remains unclear.

Methods: The expression of OLFML3 in the placenta and important clinical indicators were performed, followed by a correlation analysis. The effect of OLFML3 on the behavior of HTR-8/SVneo cells was examined, and the downstream molecular mechanisms of OLFML3 were investigated in HTR-8/SVneo cells. Additionally, a rat model of PE was generated by adenovirus injection via the tail vein to verify the role of OLFML3.

Results: OLFML3 is highly expressed in both syncytiotrophoblasts and cytotrophoblasts and deregulated in preeclamptic placentas. OLFML3 overexpression in HTR-8/SVneo cells promoted cell proliferation, migration, invasion, and impeded Apoptosis, and triggered phosphorylation on ser473 of Akt. Conversely, OLFML3 knockdown exerted opposite effects. Furthermore, OLFML3 overexpression ameliorates CoCl2-induced Apoptosis of HTR-8/SVneo cells. In a rat model, OLFML3 overexpression alleviates PE-associated maternal symptoms, leading to lower blood pressure, less severe proteinuria, improved fetal growth restriction, as well as upregulation of P-AKT and downregulation of Cleaved caspase3 and Bax.

Discussion: OLFML3 may alleviate PE development by inhibiting extravillous trophoblast cell Apoptosis through the PI3K/Akt pathway. Our findings indicated that OLFML3 may provide a possible therapeutic target for PE.

Keywords

Apoptosis; OLFML3; PI3K/AKT; Preeclampsia; RNA sequencing.

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