TPM2 as a novel inflammatory regulator in severe obstetric disorders: Integrative bioinformatics and functional
Zonggao Liao1, Fei Zhao1, Yao Li1
1MICU, Jiangxi Maternal and Child Health Hospital, Nanchang, Jiangxi 330006, China.
Background And Objective:
Severe obstetric disorders, such as preeclampsia and severe maternal infections, are major contributors to maternal and perinatal morbidity. Inflammation plays a central role in their pathogenesis, yet the underlying molecular regulators remain poorly defined. We sought to uncover key genes and signaling pathways involved in inflammatory responses of severe obstetric disorders through integrated bioinformatics and functional validation.
Methods:
The identification of differentially expressed genes (DEGs) was performed through the integration of transcriptomic datasets (GSE131411 as well as GSE233557), which subsequently underwent a series of analyses such as protein-protein interaction (PPI) network development, enrichment analysis,and single-sample gene set enrichment analysis(ssGSEA). Key genes were validated using qRT-PCR and Western blot in placental tissues and LPS-treated HTR-8/SVneo cells. Functional roles were assessed through cell migration, invasion, cytokine secretion, and NF-κB signaling assays.
Results:
TPM2 and DAW1 were significantly downregulated in inflammatory conditions, with TPM2 showing stronger involvement (P < 0.01). TPM2 overexpression enhanced trophoblast migration and invasion as well as suppressed IL-6, IL-1β, and IL-8 production (P < 0.01). Mechanistically, TPM2 inhibited IκBα degradation and blocked nuclear translocation of p65 (P < 0.01), thereby suppressing NF-κB signaling.
Conclusion:
TPM2 is a novel modulator of inflammation in severe obstetric disorders. These findings offer mechanistic insights and highlight TPM2's potential as a diagnostic biomarker and therapeutic target in inflammatory pregnancy complications.
