OLFML3 suppresses trophoblast apoptosis via the PI3K/AKT pathway: A possible therapeutic target in preeclampsia
Placenta(2024)
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.
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Key words
Preeclampsia,RNA sequencing,OLFML3,Apoptosis,PI3K/AKT
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