Work

Enoxaparin alleviates preeclampsia by enhancing trophoblast function via the NSUN2-mediated m5C methylation of PAX3 mRNA

Year: 2025

Type: article

Abstract: Preeclampsia (PE), a complex multisystem disorder, is a major contributor to maternal and perinatal morbidity and mortality. Enoxaparin, a low-molecular-weight heparin, has shown therapeutic efficacy in preventing various diseases. This study aimed to investigate the role of enoxaparin in PE and clarify its underlying mechanisms. Trophoblast (HTR-8/SVneo) cell viability, proliferation, migration, and invasion under hypoxia were assessed by Cell Counting Kit-8 (CCK-8), EdU incorporation, wound healing, and Transwell assays. Global RNA m 5 C levels were measured via dot blot. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was employed to quantify mRNA levels of RNA methyltransferases. The interaction between NOL1/NOP2/SUN domain-containing protein 2 (NSUN2) and paired box 3 (PAX3) was examined via RNA immunoprecipitation (RIP) assays. Additionally, 5-methylcytosine (m 5 C) sites in PAX3 were analyzed using a dual-luciferase reporter assay. A PE mouse model was established to validate findings. Enoxaparin enhanced trophoblast proliferation, migration, and invasion under hypoxia. It upregulated the m 5 C methyltransferase NSUN2 and increased global RNA m 5 C levels. Clinically, NSUN2 and global m 5 C levels were reduced in PE placentas. NSUN2 knockdown suppressed trophoblast function and abolished enoxaparin’s benefits. Mechanistically, NSUN2 bound to PAX3 mRNA and installed m 5 C methylation, which stabilized PAX3 transcripts and promoted its expression. PAX3 overexpression rescued the impairments caused by NSUN2 knockdown. In mice, enoxaparin ameliorated hypertension, proteinuria, placental injury, and elevated fms-like tyrosine kinase-1 (sFLT-1), effects reversed by NSUN2 silencing. Enoxaparin mitigated PE progression by upregulating NSUN2, which enhanced PAX3 expression via site-specific m 5 C methylation, thereby improving trophoblast function. The NSUN2/m 5 C/PAX3 axis represents a novel mechanistic insight and potential therapeutic target for PE.

Source: European journal of medical research

DOI: 10.1186/s40001-025-03548-6

Authors: Xuan Zhong, Danfeng Zeng

Institutions: Shantou University Medical College, Second Affiliated Hospital of Shantou University Medical College

Language: English

Topic: Pregnancy and preeclampsia studies

Subfield: Obstetrics and Gynecology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,190