title: LPS increases MUC5AC by TACE/TGF-α/EGFR pathway in human intrahepatic biliary epithelial cell.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, No. 29 Gaotanyan Street, Shapingba District, Chongqing 400038, China ; The 306th Hospital of PLA, No. 9 Anxiang Road (N), Chaoyang District, Beijing 100101, China.
authors.forename: Zipei
authors.initials: Z
authors.lastname: Liu
authors.forename: Feng
authors.initials: F
authors.lastname: Tian
authors.forename: Xiaobin
authors.initials: X
authors.lastname: Feng
authors.forename: Yu
authors.initials: Y
authors.lastname: He
authors.forename: Peng
authors.initials: P
authors.lastname: Jiang
authors.forename: Jianwei
authors.initials: J
authors.lastname: Li
authors.forename: Fei
authors.initials: F
authors.lastname: Guo
authors.forename: Xin
authors.initials: X
authors.lastname: Zhao
authors.forename: Hong
authors.initials: H
authors.lastname: Chang
authors.forename: Shuguang
authors.initials: S
authors.lastname: Wang
mesh_terms: D051722:ADAM Proteins / Q000096:biosynthesis* / Q000235:genetics; D000072198:ADAM17 Protein; D001653:Bile Ducts, Intrahepatic / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008070:Lipopolysaccharides / Q000633:toxicity; D020347:Lithiasis / Q000235:genetics / Q000473:pathology*; D055271:Mucin 5AC / Q000096:biosynthesis*; D015398:Signal Transduction / Q000187:drug effects; D016211:Transforming Growth Factor alpha / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D008070:Lipopolysaccharides; C524678:MUC5AC protein, human; D055271:Mucin 5AC; D016211:Transforming Growth Factor alpha; C512478:EGFR protein, human; D066246:ErbB Receptors; D051722:ADAM Proteins; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human
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