DEHP induces hepatic fibrosis through STAT3-SLC7A11-ROS axis

Area of Science:

• Environmental toxicology
• Molecular biology
• Hepatology

Background:

• Di-(2-ethylhexyl) phthalate (DEHP) is a common environmental contaminant linked to liver disease progression.
• The exact molecular mechanisms of DEHP-induced liver fibrosis are not fully understood.

Purpose of the Study:

• To investigate the effects of DEHP on liver fibrosis.
• To elucidate the underlying molecular mechanisms of DEHP-induced liver fibrosis.

Main Methods:

• Exposure of human hepatic stellate cells (HSCs) to DEHP.
• Analysis of fibrosis markers (α-SMA).
• Bioinformatic analysis including protein-protein interaction (PPI) network and pathway mapping.
• Molecular docking simulations.
• Assessment of reactive oxygen species (ROS) levels and SLC7A11 expression.

Main Results:

• DEHP exposure activated HSCs and upregulated α-SMA.
• DEHP-induced liver fibrosis is associated with ROS accumulation.
• DEHP binds to STAT3, downregulating SLC7A11 expression and promoting ROS accumulation via the STAT3-SLC7A11-ROS axis.

Conclusions:

• DEHP promotes liver fibrosis by inducing intracellular ROS accumulation through the STAT3-SLC7A11-ROS signaling pathway.
• This study identifies novel molecular targets for preventing and treating DEHP-induced liver fibrosis.