DNA methylation and MeCP2 regulation of PTCH1 expression during rats hepatic fibrosis

Cell Signal. 2013 May;25(5):1202-11. doi: 10.1016/j.cellsig.2013.01.005. Epub 2013 Jan 16.


Hepatic stellate cell (HSC) activation plays an important role in liver fibrogenesis. Transdifferentiation of quiescent hepatic stellate cells into myofibroblastic-HSCs is a key event in liver fibrosis. The methyl-CpG-binding protein MeCP2 which promotes repressed chromatin structure is selectively detected in myofibroblasts of diseased liver. MeCP2 binds to methylated CpG dinucleotides, which are abundant in the promoters of many genes. Treatment of HSCs with DNA methylation inhibitor 5-aza-2'- deoxycytidine (5-azadC) prevented proliferation and activation. Treatment with 5-azadC prevented loss of Patched (PTCH1) expression that occurred during HSCs activation. In a search for underlying molecular medchanisms, we investigated whether the targeting of epigenetic silencing mechanisms could be useful in the treatment of PTCH1-associated fibrogenesis. It was indicated that hypermethylation of PTCH1 is associated with the perpetuation of fibroblast activation and fibrosis in the liver. siRNA knockdown of MeCP2 increased the expressions of PTCH1 mRNA and protein in hepatic myofibroblasts. These data suggest that DNA methylation and MeCP2 may provide molecular mechanisms for silencing of PTCH1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Azacitidine / analogs & derivatives
  • Azacitidine / pharmacology
  • Carbon Tetrachloride / toxicity
  • Cell Line
  • Cell Transdifferentiation
  • DNA Methylation*
  • Gene Expression / drug effects
  • Hepatic Stellate Cells / cytology
  • Hepatic Stellate Cells / drug effects
  • Immunohistochemistry
  • Kruppel-Like Transcription Factors / metabolism
  • Liver Cirrhosis / chemically induced
  • Liver Cirrhosis / metabolism*
  • Liver Cirrhosis / pathology
  • Male
  • Methyl-CpG-Binding Protein 2 / antagonists & inhibitors
  • Methyl-CpG-Binding Protein 2 / genetics
  • Methyl-CpG-Binding Protein 2 / metabolism*
  • Myofibroblasts / cytology
  • Myofibroblasts / metabolism
  • Patched Receptors
  • Patched-1 Receptor
  • Promoter Regions, Genetic
  • Protein Binding
  • RNA Interference
  • RNA, Messenger / metabolism
  • RNA, Small Interfering / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism*
  • Zinc Finger Protein GLI1


  • Gli1 protein, rat
  • Kruppel-Like Transcription Factors
  • Methyl-CpG-Binding Protein 2
  • Patched Receptors
  • Patched-1 Receptor
  • Ptch1 protein, rat
  • RNA, Messenger
  • RNA, Small Interfering
  • Receptors, Cell Surface
  • Zinc Finger Protein GLI1
  • 5-aza-2'-deoxycytidine-5'-monophosphate
  • Carbon Tetrachloride
  • Azacitidine