Transforming Growth Factor Beta has Dual Effects on MMP9 and uPA Expression in HTR-8/SVneo Human Trophoblastic Cell Line

Abstract

Invasion of trophoblast into endometrium is vital for successful pregnancy development. MMP9 and uPA are key proteases in this process, but it is still not clear the regulation of its expression by Transforming Growth Factor Beta (TGF-β), known negative regulator of trophoblast invasion. We evaluated the effect of TGF-β on the transcriptional expression of uPA and MMP9 over time, in HTR- /SVneo trophoblast cells cultured with or without 0.5 % fetal bovine serum, via RT qPCR. The involved transcription factors and signaling pathways were analyzed in silico, using Proscan, Enrich, PCViz and WikiPathway. Results showed that that TGF-β regulates the expression of uPA and MMP9. Serum modified the nature of TGF-β’s effects on uPA expression, from negative without serum to positive with it, showing opposite effects on MMP9 expression. In silico analysis evidenced different transcription factors for each protease, some belonging to TGF-β ssignaling pathway, and crosstalk with MAPK and Wnt/β-catenin pathways. The TGF-β ddual role is discussed proposing that serum affects the cellular context. Transcriptional regulation of MMP9 and uPA by TGF-β is differential and depends on serum presence and evaluation time.