The involvement of p38 MAPK in transforming growth factor beta1-induced apoptosis in murine hepatocytes

Cell Res. 2001 Jun;11(2):89-94. doi: 10.1038/sj.cr.7290072.

Abstract

We reported in this manuscript that TGF-beta1 induces apoptosis in AML12 murine hepatocytes, which is associated with the activation of p38 MAPK signaling pathway. SB202190, a specific inhibitor of p38 MAPK, strongly inhibited the TGF-beta1-induced apoptosis and PAI-1 promoter activity. Treatment of cells with TGF-beta1 activates p38. Furthermore, over-expression of dominant negative mutant p38 also reduced the TGF-beta1-induced apoptosis. The data indicate that the activation of p38 is involved in TGF-beta1-mediated gene expression and apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / physiology*
  • Cells, Cultured / drug effects
  • DNA Fragmentation / drug effects
  • DNA Fragmentation / physiology
  • Enzyme Inhibitors / pharmacology
  • Gene Expression Regulation, Enzymologic / drug effects
  • Gene Expression Regulation, Enzymologic / physiology
  • Genes, Reporter / drug effects
  • Genes, Reporter / physiology
  • Genetic Vectors / drug effects
  • Genetic Vectors / physiology
  • Hepatocytes / cytology
  • Hepatocytes / drug effects
  • Hepatocytes / metabolism*
  • Imidazoles / pharmacology
  • MAP Kinase Signaling System / drug effects
  • MAP Kinase Signaling System / physiology*
  • Mice
  • Mitogen-Activated Protein Kinases / drug effects
  • Mitogen-Activated Protein Kinases / genetics
  • Mitogen-Activated Protein Kinases / metabolism*
  • Mutation / drug effects
  • Mutation / physiology
  • Phosphorylation / drug effects
  • Plasminogen Activator Inhibitor 1 / genetics
  • Pyridines / pharmacology
  • Transfection
  • Transforming Growth Factor beta / metabolism*
  • Transforming Growth Factor beta / pharmacology
  • Transforming Growth Factor beta1
  • p38 Mitogen-Activated Protein Kinases

Substances

  • Enzyme Inhibitors
  • Imidazoles
  • Plasminogen Activator Inhibitor 1
  • Pyridines
  • Tgfb1 protein, mouse
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • 4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole