Matrix Metalloproteinase 7 Mediates Epithelial-Mesenchymal Transition to Promote Liver Fibrosis Through E-cadherin/β-catenin Pathway in Biliary Atresia

Biliary atresia (BA) is characterized by rapidly progressive hepatic fibrosis with unclear mechanisms. This study aimed to investigate the role of matrix metalloproteinase 7 (MMP7) in this process and its potential for targeted therapy. Serum and liver tissue samples from BA patients were collected to analyze the correlation between MMP7 and liver fibrosis. Gene set enrichment analysis (GSEA) based on GEO datasets was performed to explore MMP7-associated biological processes. Clinical samples were further used to examine the relationship between MMP7 and epithelial-mesenchymal transition (EMT) in biliary epithelial cells (BECs). The effects of MMP7 on BECs and the underlying mechanisms were validated in vitro. Finally, the profibrotic effects and therapeutic potential of MMP7 were explored in chronic BA mice. Results showed that MMP7 was positively correlated with liver fibrosis in BA patients. GSEA revealed that MMP7 was most significantly associated with EMT, which was further validated by EMT scoring in intrahepatic BECs of patients. In vitro, MMP7 induced EMT in BECs by cleaving E-cadherin and promoting β-catenin nuclear translocation. Blockade of MMP7 alleviated EMT and liver fibrosis in BA mice. In conclusion, MMP7 promotes liver fibrosis in BA by driving EMT via the E-cadherin/β-catenin pathway, and targeting MMP7 demonstrates anti-fibrotic effects.

biliary atresia; chronic biliary atresia model; epithelial–mesenchymal transformation; liver fibrosis; matrix metalloproteinase-7.