Abstract / Summary
Abstract Inflammatory signaling in the human myometrium drives uterine activation and labor, yet its transcriptional regulation remains incompletely understood. We previously identified MAFF as an inflammation-inducible transcription factor in human myometrial cells. Here, we investigated whether FOS regulates MAFF expression and whether MAFF contributes to myometrial cell contractility. FOS knockdown increased MAFF mRNA approximately 1.5-fold under basal conditions and 1.7-fold following IL1B stimulation, accompanied by increased MAFF protein after 1 h of IL1B exposure. ChIP-qPCR demonstrated FOS occupancy in the MAFF promoter region, supporting a negative regulatory relationship. Functionally, CRISPR/Cas9-generated MAFF-deficient cells displayed approximately 15–25% lower basal contractility than wild-type cells. Contractile responses to IL1B varied among the MAFF-deficient clones, although they generally remained less contractile than wild-type cells. MAFF overexpression increased contraction in wildtype cells (by 7%) and two of three MAFF-deficient clones (by 4–8%). Conversely, FOS overexpression reduced contraction in wild-type cell (−6.7%) but had no significant effect in the MAFF-deficient clones. Together, these findings identify FOS as a negative regulator of MAFF expression and support a role for MAFF in modulating myometrial cell contractility.