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BioMed Research International
Volume 2013, Article ID 165715, 8 pages
Research Article

LPS Increases MUC5AC by TACE/TGF-α/EGFR Pathway in Human Intrahepatic Biliary Epithelial Cell

1Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, No. 29 Gaotanyan Street, Shapingba District, Chongqing 400038, China
2The 306th Hospital of PLA, No. 9 Anxiang Road (N), Chaoyang District, Beijing 100101, China

Received 4 April 2013; Revised 15 July 2013; Accepted 18 July 2013

Academic Editor: Dimitrios P. Bogdanos

Copyright © 2013 Zipei Liu et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Background. Mucin 5AC (MUC5AC) overproduction plays important roles in stone formation and recurrence of hepatolithiasis. We aim to investigate the involved mechanism and the potential target to block this process. Methods. 42 bile duct samples from hepatolithiasis and 15 normal bile duct samples from hemangioma patients were collected for detecting MUC5AC expression by immunohistochemistry. MUC5AC and phosphoepidermal growth factor receptor (pEGFR) expressions in human intrahepatic biliary epithelial cells (HIBECs) cultured with or without lipopolysaccharide (LPS) were detected by real-time PCR and western blot analysis. Transforming growth factor-α (TGF-α) secretion in HIBECs was detected by ELISA. Results. MUC5AC was overexpressed in bile ducts of hepatolithiasis samples compared with bile ducts from hemangioma samples. LPS upregulated MUC5AC expression in HIBECs. LPS promoted EGFR activation, and inhibiting EGFR activation by AG1478 significantly decreased LPS-induced MUC5AC overexpression in HIBECs. Moreover, LPS increased TGF-α secretion, and inhibiting tumor necrosis factor-α converting enzyme (TACE), which has been implicated in ectodomain cleavage of TGF-α, significantly inhibited LPS-induced EGFR activation and subsequent MUC5AC overexpression in HIBECs. Conclusion. Our results suggested that LPS increases MUC5AC expression through the TACE/TGF-α/EGFR pathway in HIBECs. This new finding might give light to the prevention of stone formation and recurrence of hepatolithiasis.