Activation of the Integrin αV-YAP-CTGF Axis in Liver Sinusoidal Endothelial Cells Promotes Liver Fibrogenesis, Leading to Portal Hypertension and Liver Carcinogenesis in Congestive Hepatopathy - PubMe
3 hours ago
- #Liver Fibrosis
- #YAP-CTGF Axis
- #Mechanotransduction
- Chronic liver congestion leads to fibrosis, cirrhosis, and cancer.
- Study focuses on liver sinusoidal endothelial cells (LSECs) in congestive hepatopathy (CH).
- Partial inferior vena cava ligation (pIVCL) induced hepatic congestion in mice.
- Single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics were used.
- Integrin signaling and YAP activation observed in pericentral LSECs post-pIVCL.
- Connective tissue growth factor (CTGF) was the most upregulated gene in LSECs.
- Hydrostatic pressure activated YAP via integrin αV, increasing CTGF and COL4 in LSECs.
- LSEC-derived CTGF upregulated COL1 and COL4 in hepatic stellate cells.
- CTGF knockout in endothelial cells reduced fibrosis, portal hypertension, and tumorigenesis.
- Integrin αV inhibition decreased CTGF, COL4, and COL1, alleviating fibrosis and hypertension.
- Human Fontan-associated liver disease samples showed YAP activation and CTGF upregulation.
- CTGF in LSECs plays a key role in CH fibrogenesis.
- The integrin αV-YAP-CTGF axis is a potential therapeutic target for CH.