DExD-Box Helicase 21 Enhances Myometrial Contractions Through Thrombospondin-1-Mediated Increase in Cell Adhesion

During labour, the myometrium transitions from a quiescent to an actively contracting state, governed by changes in gene expression. Identifying the pivotal transcription regulators involved in these gene expression alterations offers a useful strategy for addressing abnormal myometrial contractions. This study determined that the transcriptional regulator DExD-Box Helicase 21 (DDX21) is upregulated in human myometrial tissues and myometrial smooth muscle cells (hMSMCs) during labour. DDX21 enhances hMSMC contractility through a mechanism that involves binding to thrombospondin 1 (THBS1) mRNA, a cell adhesion molecule, and promoting its transcription and subsequent protein expression. This upregulation of THBS1 increases cellular adhesion, which is crucial for effective myometrial contraction and for contractile function. Consequently, the DDX21-THBS1 pathway could be a potential target for modulating key functions required for effective myometrial contraction.