ORIGINAL RESEARCH article
Front. Genet.
Sec. Immunogenetics
Integrative biology shows DPP4 affects inflammatory response to eclampsia and cell model growth via p65/NLRP3/ASC/Caspase-1 pathway
Provisionally accepted
- Shijiazhuang Obstetrics and Gynecology Hospital, Shijiazhuang, China
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Eclampsia exerts a profound influence on maternal and neonatal health, accounting for a considerable fraction of emergency department presentations, maternal fatalities, and enduring complications. The ascertainment of dependable biomarkers is imperative for augmenting the diagnosis, prophylaxis, and administration of eclampsia. We began by conducting a differential gene expression analysis on the GSE60438 dataset, revealing that 4,642 genes were upregulated and 2,193 genes were downregulated in pre-eclampsia samples. WGCNA identified nine gene modules, with the red module showing the strongest positive correlation and the magenta module exhibiting a negative correlation with pre-eclampsia. GO analysis highlighted significant enrichment of pre-eclampsia-associated genes in processes such as chromosome organization, mitochondrial function, and DNA repair. GSEA further identified key immune-related pathways, including cytokine production and chemokine signaling. Additionally, immune cell infiltration was assessed using the xCell algorithm. Through LASSO regression, we pinpointed DPP4 as a central gene. This finding was validated by RT-qPCR and Western blot, which showed significant upregulation of DPP4 in placental tissues and serum from pre-eclampsia patients. In cellular models, DPP4 knockdown markedly reduced the levels of pro-inflammatory cytokines IL-6 and TNF-α, implicating DPP4 in the inflammatory response characteristic of pre-eclampsia. Functional assays demonstrated that DPP4 inhibition significantly impaired migration, invasion, and lumen formation in HTR-8 cells, underscoring its crucial role in trophoblast cell function. Finally, we examined the p65/NLRP3/ASC/Caspase-1 signaling pathway and observed a significant decrease in the phosphorylation of p65, NLRP3, ASC, and Caspase-1 following DPP4 knockdown, indicating that DPP4 modulates inflammation via this pathway. In conclusion, we found that targeting DPP4 may be an innovative strategy to regulate inflammatory signalling in eclampsia, with the potential to alleviate maternal symptoms and improve pregnancy outcomes.
Keywords: DPP4, Eclampsia, Growth, Inflammatory Response, Pathway
Received: 24 Dec 2025; Accepted: 04 Feb 2026.
Copyright: © 2026 Bian, Hao, Yang and Sun. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Jianghui Sun
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