Particle.news
Download on the App Store

Pressure-Responsive Pathway Ties Liver Congestion to Fibrosis and Cancer

Blocking integrin αV or CTGF in mice lessened congestion-induced liver damage, suggesting druggable targets.

Overview

  • The study, published in Gastroenterology (2026; DOI: 10.1053/j.gastro.2025.11.014), maps a mechanosensitive axis in liver sinusoidal endothelial cells.
  • Increased hydrostatic pressure activated integrin αV, which triggered YAP signaling and upregulated CTGF in these endothelial cells.
  • In vitro assays and a mouse congestion model showed that this cascade promotes fibrogenesis, portal hypertension, and tumorigenesis.
  • Pharmacologic inhibition of integrin αV or endothelial CTGF knockout improved disease measures in mice.
  • Single-cell and spatial transcriptomics in human livers, including Fontan-associated cases, revealed the same YAP/CTGF activation pattern, supporting translational potential.