LPS increases MUC5AC by TACE/TGF-α/EGFR pathway in human intrahepatic biliary epithelial cell.
LPS increases MUC5AC by TACE/TGF-α/EGFR pathway in human intrahepatic biliary epithelial cell.
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DOI：
10.1155/2013/165715
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发表时间：
2013
影响因子：
--
通讯作者：
Wang S
中科院分区：
文献类型：
--
作者：
Liu Z;Tian F;Feng X;He Y;Jiang P;Li J;Guo F;Zhao X;Chang H;Wang S
背景粘蛋白5AC（MUC 5AC）的过度表达在肝内胆管结石的形成和复发中起重要作用。我们的目的是探讨其机制和潜在的目标，以阻止这一进程。方法.采用免疫组织化学方法检测42例肝胆管结石患者和15例肝血管瘤患者的正常胆管组织中MUC 5AC的表达。采用实时荧光定量PCR和Western blot方法检测脂多糖（LPS）刺激和不刺激培养的人肝内胆管上皮细胞（HIBECs）中MUC 5AC和磷酸化表皮生长因子受体（pEGFR）的表达。ELISA法检测转化生长因子-α（TGF-α）的分泌。结果肝胆管结石标本中MUC 5AC的表达高于肝血管瘤标本中MUC 5AC的表达。LPS可上调HIBEC中MUC 5AC的表达。LPS促进EGFR活化，AG 1478抑制EGFR活化显著降低LPS诱导的HIBECs中MUC 5AC过表达。此外，LPS增加TGF-α分泌，并抑制肿瘤坏死因子-α转化酶（TACE），这已涉及在TGF-α的胞外域切割，显着抑制LPS诱导的EGFR激活和随后MUC 5AC在HIBEC中的过表达。结论我们的结果表明LPS通过TACE/TGF-α/EGFR途径增加HIBECs中MUC 5AC的表达。这一新发现可能对预防肝内胆管结石的形成和复发有一定的意义。
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.
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影响因子：
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