Integrin αV–YAP–CTGF Signaling Links Congestion to Fibrosis and Cancer

A Gastroenterology study used single-cell and spatial transcriptomic mapping in liver sinusoidal endothelial cells (LSECs) in a mouse model of chronic hepatic congestion, alongside analyses of human liver samples.

Investigators described a molecular pathway linking congestion-related changes in LSECs with disease features discussed in the report, including liver fibrosis, portal hypertension, and liver tumorigenesis. The central finding was described as an integrin αV–YAP–CTGF signaling axis in LSECs that appears to connect liver congestion to fibrosis.

A mechanistic sequence from laboratory experiments examined how physical forces in congestion might be sensed by LSECs. Using LSECs grown in the laboratory, investigators reported that increased hydrostatic pressure—framed as analogous to pressure conditions during chronic congestion—activated YAP through integrin αV. The research then describes this YAP activation as being followed by CTGF upregulation in LSECs. Overall, the experiments were presented as linking pressure exposure to an integrin-linked YAP response with CTGF upregulation in LSECs.

Preclinical perturbation experiments in the mouse congestion model were also supportive of the pathway’s role in the described phenotype. Specifically, the article reports that inhibiting integrin αV or knocking out CTGF in LSECs was associated with improved outcomes in the model, framed within the report as changes consistent with mitigation of congestion-associated liver injury features discussed by the authors. These interventions were described as candidate nodes within the integrin αV–YAP–CTGF cascade rather than as clinical strategies, with the mouse model providing the context for the reported improvements. The intervention observations were presented as aligning with the proposed contribution of the integrin αV–YAP–CTGF pathway to disease features in congestive hepatopathy models.

Human tissue analyses were described as providing cross-species corroboration at the level of measurable pathway signals in LSECs. Single-cell and spatial transcriptomic profiling of liver samples from patients with chronic liver congestion showed a similar pattern to that observed in mice, including YAP activation in LSECs alongside increased CTGF levels. In that framing, YAP activity and CTGF expression functioned as observed molecular signatures in patient samples rather than as proposed clinical tests.

Key Takeaways:

• The article reports that single-cell and spatial transcriptomic mapping in LSECs across a mouse congestion model and human liver samples described a similar signaling pattern.
• In the laboratory experiments, pressure exposure was described as linking integrin αV to YAP activation with CTGF upregulation in LSECs.
• The report describes improved mouse-model outcomes with integrin αV inhibition or LSEC-specific CTGF knockout, alongside similar YAP/CTGF activation signals observed in patient samples.