Background: Proper invasion and migration of trophoblasts are critical for successful human pregnancy. Tumor necrosis factor-α (TNF-α) has two biologically active forms: the membrane-bound TNF-α (mTNF) and the soluble TNF-α (sTNF).
Objective: To investigate the role of both forms of TNF-α in trophoblasts invasion and migration and to elucidate their underlying mechanisms.
Methods: We exposed HTR-8/SVneo trophoblasts to exogenous mTNF or sTNF and evaluated their cellular behaviors. Proliferation was assessed using a Cell Counting Kit-8, while invasion and migration were assessed through Transwell assays. Additionally, we measured mRNA levels of matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinases-1 (TIMP-1), and plasminogen activator inhibitor-1 (PAI-1) using qRT-PCR. The expression of IκB-α was determined by western blot analysis.
Results: Unlike sTNF, mTNF enhances the invasion and migration of trophoblasts. Mechanistic analysis showed that mTNF increased MMP-9 expression while decreasing TIMP-1 and PAI-1 expression, and it inhibited the activation of NF-κB signaling pathway in HTR-8/SVneo cells with or without lipopolysaccharide (LPS) treatment.
Conclusion: This research uncovered a new function of mTNF in regulating trophoblast invasion and migration, offering a new approach to treating pregnancy-related diseases associated with inadequate trophoblast invasion.