Focal adhesion kinase signaling is necessary for the hydrogen sulfide-enhanced proliferation, migration, and invasion of HTR8/SVneo human trophoblasts

Abstract

Objective: Hydrogen sulfide (H2S) has been elucidated that it promotes migration and invasion in human placenta trophoblasts. However, the signaling pathway underlying H2S-based regulation of trophoblasts remains unknown. Hence, we investigated the potential effect of sodium hydrosulfide (NaHS), an exogenous H2S donor, on extravillous trophoblasts. Methods: The Cell Counting Kit-8 was used to detect the proliferative activity of trophoblasts and to screen the optimal concentration of NaHS. The migration and invasion of HTR8/SVneo cells were measured by Transwell assays. Gene expression was determined by quantitative real-time PCR analysis. Protein expression was determined by western blot. Results: We found that NaHS could promote the proliferation, migration, and invasion of HTR8/SVneo cells. The phosphorylation of focal adhesion kinase (FAK), Src, and extracellular signal-regulated kinase (ERK) were activated by NaHS. Moreover, NaHS also upregulated the expression of matrix metalloproteinase-2 (MMP-2) and MMP-9, downregulated the expression of E-cadherin in HTR8/SVneo cells. The application of NaHS could increase the expression of cystathionine-β-synthase. Conclusion: Both FAK–Src signaling and the upstream signaling cascade of ERK activation play a significant important role in NaHS-induced proliferation, migration, and invasion via upregulating activity of MMP-2, MMP-9, and downregulating E-cadherin in HTR8/SVneo cells. These novel findings may provide a strong foundation for the clinical application of H2S donor drugs.