OLFML3 suppresses trophoblast apoptosis via the PI3K/AKT pathway: A possible therapeutic target in preeclampsia.
Placenta
; 147: 1-11, 2024 Mar 06.
Article
in En
| MEDLINE
| ID: mdl-38277999
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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pre-Eclampsia
/
Glycoproteins
/
Intercellular Signaling Peptides and Proteins
/
Proto-Oncogene Proteins c-akt
Type of study:
Prognostic_studies
Limits:
Animals
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Female
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Humans
/
Pregnancy
Language:
En
Journal:
Placenta
Year:
2024
Document type:
Article
Affiliation country:
China