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Updated: Sep 16, 2025
A Mouse Model of Chronic Liver Fibrosis for the Study of Biliary Atresia
Published on: February 3, 2023
Dual Functions and Therapeutic Potential of FZD6 in Biliary Atresia
Xinying Wang1, Hongkun Lai1, Ledong Tan1
1Department of Pediatric Surgery, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510000, China.
Objective:
Biliary atresia (BA), a severe neonatal cholangiopathy, lacks pharmacological therapies. This study aimed to identify causal genes and therapeutic targets through multi-omics analyses, emphasizing FZD6's role in immune-pathological mechanisms.
Methods:
Mendelian randomization (MR) and GWAS prioritized BA-associated genes. Co-localization, ceRNA network construction, transcriptomic profiling (GSE46960: 64 BA vs 17 controls), and immune infiltration (ssGSEA/CIBERSORT) were conducted. Immunohistochemistry validated FZD6 expression. Molecular docking (CB-Dock2) screened FZD6-targeting drugs.
Results:
MR identified four causal genes (GSR, PGAP6, FZD6, FGD4). FZD6 was upregulated in BA tissues (Wilcoxon p = 0.00021) and correlated with immune dysregulation, including central memory CD4 T cells (r = 0.66, **p < 0.01) and T follicular helper cells (r = 0.36, *p < 0.05). Machine learning identified CD56dim NK cells and mast cells as key immune drivers. Immunohistochemistry confirmed FZD6 overexpression in BA bile ducts. Molecular docking identified dexamethasone (- 9.8 kcal/mol) and gomisin N (- 9.5 kcal/mol) as high-affinity FZD6 ligands.
Conclusion:
This study establishes FZD6 as a novel therapeutic target in BA, linking its dysregulation to immune-mediated bile duct injury. Multi-omics integration advances BA pathogenesis understanding, while drug candidates offer translational potential.
