PAI-1 as a modulator of the EMT-associated signaling pathway during HCV protein expression.

INTRODUCTION AND

OBJECTIVES

Hepatitis C virus (HCV) infection promotes liver fibrosis through mechanisms involving epithelial-mesenchymal transition (EMT). Plasminogen activator inhibitor-1 (PAI-1), encoded by the SERPINE1 gene, is a known modulator of EMT and is upregulated during HCV infection. This study aimed to explore the contribution of PAI-1 silencing to EMT-related biomarker regulation in the context of HCV protein expression.

MATERIALS AND

METHODS

Huh7 cells were transfected with plasmids encoding HCV Core or NS5A proteins and subjected to SERPINE1 silencing. Some EMT-related biomarkers (TGFβ1, vimentin, E-cadherin) and viral protein levels were assessed by Western blot and nanoluciferase assays. Bioinformatic analysis of RNA-seq public datasets was performed to evaluate SERPINE1 expression in liver fibrosis stages and HCV-infected hepatocytes in vitro.

RESULTS

In vitro assays revealed that PAI-1 silencing is associated with the downregulation of E-cadherin and the upregulation of vimentin and TGFβ1 in both Core- and NS5A-expressing Huh7 cells. Temporal analyses confirmed that PAI-1 silencing is related to vimentin and TGFβ1 overexpression over time. Bioinformatic analysis revealed SERPINE1 expression increased with liver fibrosis severity and was elevated in HCV-infected hepatocytes. It showed strong positive correlations with genes involved in EMT.

CONCLUSIONS

Our data indicate that PAI-1 may contribute to the modulation of certain EMT-related biomarkers during HCV protein expression in Huh7 cells. These findings highlight PAI-1 as a possible target for the modulation of EMT and fibrosis progression in chronic HCV infection.