Analysis of Biliary Epithelial-Mesenchymal Transition in Portal Tract Fibrogenesis in Biliary Atresia
- Deng, Yu-Hua
- Pu, Cong-Lun
- Li, Ying-Cun
- Zhu, Jin
- Xiang, Chunping
- Zhang, Ming-Man
- Guo, Chun-Bao
Abstract
Background
The cellular origin of myofibroblast in the liver fibrosis remains unclear. This study was designed to investigate whether biliary epithelial cells (BECs) undergoing epithelial-mesenchymal transition (EMT) might be found in patients with biliary atresia, thereby serving as a source of fibrotic myofibroblasts.
Methods
Liver sections from patients with biliary atresia were evaluated to detect antigen for the BECs marker 4 and cytokeratin-7 (CK-7), proteins (fibroblast-specific protein 1, also known S100A4; the collagen chaperone heat shock protein 47, HSP47) characteristically expressed by cells undergoing EMT, as well as myofibroblasts marker a-smooth muscle actin (a-SMA).
Results
Normal bile ducts BECs could express CK-7 and low levels of a-SMA; they did not express S100A4 and HSP47. However, BECs from biliary atresia resulted in increased expression of a-SMA, S100A4, with concurrent transition to a fibroblast-like morphology and decreased expression of AK-7. Furthermore, BECs in biliary atresia were associated with significant bile ductular proliferation and coexpressed both epithelial and mesenchymal markers.
Conclusions
From significant histologic evidence, the BECs forming small- and medium-sized bile ducts undergoing EMT may account for prominent bile ductular proliferation and directly contribute to fibrogenesis in BA.
Abbreviations: EMT Epithelial-mesenchymal transition aSMA a-Smooth muscle actin BECs Biliary epithelial cells CK-7 Cytokeratin-7