Bradykinin Signaling Axis Promotes Inflammatory Cervical Remodeling under LPS-Induced Maternal Systemic Inflammation via MAPK-mediated PTGS2 Upregulation.

Recent perspectives have redefined cervical insufficiency as a dynamic biological process within the preterm birth continuum rather than a static "structural defect." This process involves the dynamic regulation of cervical remodeling by mechanical forces, inflammation, and immune cell crosstalk. Inflammation-associated cervical changes are now recognized as modifiable biological events. Based on this, the present study utilized a rat model of LPS-induced maternal systemic inflammation and a primary cervical mesenchymal cell culture system-integrated with transcriptomics, molecular biology, and pharmacological interventions-to systematically investigate the role of the bradykinin system and its downstream signaling in inflammation-associated cervical remodeling. Bradykinin and its metabolite des-Arg9-bradykinin, acting through BDKRB1/BDKRB2, activated the p38, ERK1/2 and JNK MAPK cascades and upregulated PTGS2 expression in cervical mesenchymal cells; in vivo, LPS increased cervical Kng1 and bradykinin levels together with PTGS2/PGE2 and Mmp9 transcripts and disorganization of the collagen matrix. These findings suggest that the bradykinin axis may contribute to inflammatory cervical remodeling by activating the MAPK pathway and upregulating PTGS2, providing a mechanistic basis for further evaluation of the bradykinin system as a candidate target in inflammation-associated cervical remodeling.