Regulation Mechanism and Function of Epimorphin in Hepatic Stellate Cell
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Medical School of Chinese PLA,Treatment and Research Center of Infectious Diseases ,Beijing 302 Hospital,Stem Cell and Regenerative Medicine Lab, Beijing Institute of Transfusion Medicine,Treatment and Research Center of Infectious Diseases ,Beijing 302 Hospital,Treatment and Research Center of Infectious Diseases ,Beijing 302 Hospital,Stem Cell and Regenerative Medicine Lab, Beijing Institute of Transfusion Medicine,Treatment and Research Center of Infectious Diseases ,Beijing 302 Hospital,Treatment and Research Center of Infectious Diseases ,Beijing 302 Hospital,Stem Cell and Regenerative Medicine Lab, Beijing Institute of Transfusion Medicine,Treatment and Research Center of Infectious Diseases ,Beijing 302 Hospital

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This work was supported by a grant from The National Natural Science Foundation of China (81200303, 81470097)

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    Abstract:

    Hepatic stellate cell(HSC), an important interstitial cell in the liver, is the main source of extracellular matrix. Epimorphin (EPM, also called syntaxin2), a mesenchymal cell surface-associated molecule expressed in HSC, has been reported that the dysfunction is related to the development, regeneration and carcinogenesis of the liver. We found that the expression of EPM was up-regulated in hepatic stellate cells in the process of hepatic fibrosis. We studied the mechanism of EPM expression changes, found that the demethylation of promoter region promoted the expression of EPM. Stable EPM-overexpression transgenic cell lines were generated by transfecting human hepatic stellate cells with plasmids. Reverse transcriptase polymerase chain reaction(PCR) analyses and Westen blot indicated that the mRNA and protein levels of EPM in the transgenic cell lines were significantly up-regulated than that in control. By MTT assay and transwell motility assay, we further confirmed that EPM induced HSC proliferation and invasion. In conclusion, the high expression of EPM in activated hepatic stellate cells is caused by DNA demethylation, and EPM can promote the proliferation and migration of hepatic stellate cells, it may be involved in hepatic fibrogenesis.

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SHI Lei, QIN En-Qiang, JIA Ya-Li, WU Dan, JIN Lei, ZENG Quan, JIANG Tian-Jun, NIE Wei-Min, YUE Wen, WANG Fu-Sheng. Regulation Mechanism and Function of Epimorphin in Hepatic Stellate Cell[J]. Progress in Biochemistry and Biophysics,2016,43(5):506-513

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History
  • Received:December 09,2015
  • Revised:March 18,2016
  • Accepted:March 23,2016
  • Online: May 20,2016
  • Published: May 20,2016