MiR-200a/ZEB1 Pathway in Liver Fibrogenesis of Biliary Atresia

Objective: Biliary atresia (BA) is characterized by progressive liver fibrosis. Epithelial-mesenchymal transition (EMT) has been implicated as a key mechanism in the pathogenesis of organ fibrosis. MiR-200a has been shown to repress EMT. We aim to explore the role of miR-200a in the fibrogenesis of BA. Methods: We obtained the plasma samples and liver samples from patients with BA or controls to examine the role of miR-200a. Histological liver fibrosis was assessed using the Ishak fibrosis scores. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was performed to detect the expression of miR-200a in plasma. We also evaluated the expression of miR-200a in liver tissues using tyramide signal amplification fluorescence in situ hybridization (TSA-FISH). The expression of EMT related proteins zinc finger E-box-binding homeobox 1 (ZEB1), E-cadherin and α-smooth muscle actin (αSMA) in the liver sections were detected by immunohistochemical staining. Results: We found that the expression of miR-200a was both elevated in the plasma and liver tissues from BA patients compared with the controls. The hepatic expression of ZEB1 and αSMA were markedly increased in the liver sections from BA patients compared to the controls, whereas E-cadherin was downregulated in the BA group. Simultaneously, we noted that the hepatic expression of miR-200a, E-cadherin and α-SMA were upregulated with the progression of liver fibrosis in the BA group, while ZEB1 was downregulated with the progression of liver fibrosis in BA patients. Conclusion: These findings suggest EMT has a critical effect on the fibrotic process of BA, and the interaction between miR-200a and ZEB1 may regulate EMT and eventually influence liver fibrogenesis of BA. Keywords—Biliary atresia, liver fibrosis, MicroRNA, epithelialmesenchymal transition, zinc finger e-box-binding homeobox 1. Yi-Hao Chen, Shu-Yin Pang and Li-Yuan Yang are with the Clinical Laboratory, Guangzhou Medical University Affiliated Guangzhou Women and Children’s Medical Center, Guangzhou 510623, Guangdong Province, China. Feng-Hua Wang and Zheng-Rong Chen are with the Department of Pathology, Guangzhou Medical University Affiliated Guangzhou Women and Children’s Medical Center, Guangzhou 510623, Guangdong Province, China. Xiao-fang Peng is with the Pediatrics Research Institute, Guangzhou Medical University Affiliated Guangzhou Women and Children’s Medical Center, Guangzhou 510623, Guangdong Province, China. Yi Chen and Bing Zhu are with the Central Laboratory, Guangzhou Medical University Affiliated Guangzhou Women and Children’s Medical Center, Guangzhou 510120, Guangdong Province, China. Hai-Ying Liu (PhD, MD) is with the Clinical Laboratory, Guangzhou Medical University Affiliated Guangzhou Women and Children’s Medical Center, No. 9 Jinsui Road, Guangzhou 510623, Guangdong Province, P. R. China (e-mail: [email protected], phone: +86-20-38076255, fax: +86-20-38076255).