Analysis of biliary epithelial-mesenchymal transition in portal tract fibrogenesis in biliary atresia.
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.
Deng
Yu-Hua
YH
Department of Hepatobiliary Surgery, Children's Hospital of Chongqing Medical University, 136 Zhongshan 2nd Rd., Chongqing, 400014, People's Republic of China.
Pu
Cong-Lun
CL
Li
Ying-Cun
YC
Zhu
Jin
J
Xiang
Chunping
C
Zhang
Ming-Man
MM
Guo
Chun-Bao
CB
D000199:Actins / Q000378:metabolism; D001652:Bile Ducts / Q000473:pathology*; D001656:Biliary Atresia / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation; D058750:Epithelial-Mesenchymal Transition; D050958:HSP47 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D053552:Keratin-7 / Q000378:metabolism; D008103:Liver Cirrhosis / Q000378:metabolism / Q000473:pathology*; D058628:Myofibroblasts / Q000378:metabolism / Q000473:pathology*; D011168:Portal System / Q000378:metabolism / Q000473:pathology; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000378:metabolism
D000199:Actins; D050958:HSP47 Heat-Shock Proteins; D053552:Keratin-7; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; C494660:SERPINH1 protein, human; C077591:S100A4 protein, human