Differential Functions of Membrane-bound and Soluble TNF-α in Regulating Trophoblasts Invasion and Migration
Chenxi Li1, Mingxin Lin1, Min Zhu1
1Department of Laboratory Medicine, Fujian Key Clinical Specialty of Laboratory Medicine, Women and Children's Hospital, School of Medicine, Xiamen University, Xiamen, Fujian, China.
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.
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