Prokineticin 2 is upregulated in preeclampsia and impairs trophoblast function.

OBJECTIVE

To investigate the role of prokineticin 2 (PK2) in the pathogenesis of preeclampsia (PE), a severe hypertensive disorder of pregnancy with incompletely understood placental mechanisms.

METHODS

The placental expression of PK2 and prokineticin receptor 2 (PKR2) was assessed by immunohistochemistry, and PK2 levels were quantified by enzyme-linked immunosorbent assay in samples from patients with PE and a PE mouse model, compared with normal controls. The functional impact of recombinant PK2 protein on proliferation and migration was assessed in the trophoblast cell line HTR-8/SVneo. Transcriptomic analysis was performed on PK2-treated cells to identify differentially expressed genes and enriched pathways.

RESULTS

PK2 and PKR2 were significantly upregulated in PE placentas. PK2 expression was significantly higher in the culture medium of primary trophoblast cells derived from PE patients and a PE mouse model than in that from normal controls. Recombinant PK2 markedly inhibited trophoblast proliferation and migration. Transcriptomic analysis revealed PK2-induced upregulation of a gene set (including EGR1, FOS, JUN, CCN1, and CCN2) with significant enrichment in stress-response and inflammatory pathways.

CONCLUSIONS

This study identifies PK2 as a key pathogenic factor in PE that impairs trophoblast function. The findings suggest that its mechanism may involve the induction of AP-1 components. Our work provides the first evidence positioning the PK2/PKR2 axis as a novel contributor to PE pathogenesis and a potential therapeutic target.