IL-1β stimulates ADAMTS9 expression and contributes to preterm prelabor rupture of membranes

• DOI: 10.1186/s12964-025-02120-3
• Publication Date: 2025-03-08T15:42:56Z
• Authors: Jiasong Cao; Yixin Wang; Qimei Lin; Shuqi Wang; Yongmei Shen; Lei Zhang; Wen Li; Ling Chen; Chunliu Liu; Shihan Yao; Ling Shuai; Xu Chen; Zongjin Li; Ying Chang
• Keywords: Rupture of membranes; Expression (computer science)

Preterm prelabor rupture of membranes (pPROM) is a leading cause neonatal morbidity and mortality. While intra-amniotic infection well-established driver pPROM, the role sterile inflammation remains unclear. Recent evidence suggests that interleukin-1 beta (IL-1β) promotes extracellular matrix (ECM) remodeling via downstream effectors, disintegrin-like metalloproteinase domain with thrombospondin type 1 motif 9 (ADAMTS9), while protein O-fucosyltransferase 2 (POFUT2) facilitates its O-fucosylation secretion, amplifying ECM degradation. This study investigates how IL-1β-triggered nuclear factor kappa-B (NF-κB) activation ADAMTS9 POFUT2 expression, ultimately driving fetal membrane weakening in pPROM without signs infection. A nested case-control included maternal serum samples from 60 pregnant women (34 26 full-term births [FTB]). ELISA measured levels IL-1β ADAMTS9, their correlations were analyzed. Mechanistic studies utilized primary human amniotic epithelial cells (hAECs) membrane-decidua explants treatment. The NF-κB was explored using chromatin immunoprecipitation (ChIP) luciferase assays to assess binding promoters POFUT2. murine model under ultrasound-guided injection used validate vitro findings pregnancy outcomes. Serum at 16 weeks gestation significantly higher cases compared FTB controls (P < 0.001). combined these biomarkers demonstrated high predictive accuracy for (AUC = 0.83). Mechanistically, activated NF-κB, promoted enhanced secretion. Together, processes drove versican degradation weakening. Intra-amniotic administration mice induced weakening, preterm birth, adverse outcomes, which mitigated by inhibitor BAY 11-7082 Maternal mid-gestation are promising non-invasive risk stratification. IL-1β-induced expression POFUT2-dependent contributing These provide new insights into potential therapeutic target pPROM.