Interleukin-1β upregulates matrix metalloproteinase-13 gene expression via c-Jun N-terminal kinase and p38 MAPK pathways in rat hepatic stellate cells.

Matrix metalloproteinase-13 (MMP-13) is crucial in the cleavage and remodeling of the extracellular matrix (ECM), and its expression levels are decreased following the induction of liver fibrosis. The aim of the present study was to investigate the role of c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) in interleukin (IL)-1β-mediated MMP-13 gene expression in rat hepatic stellate cells (HSCs). In the present study, we demonstrated that IL-1β is capable of activating JNK and p38 in a time-dependent manner and the inhibition of the JNK pathway is able to increase MMP-13 mRNA expression; however, the inhibition of the p38 MAPK pathway is capable of inhibiting MMP-13 gene expression. These data demonstrate that IL-1β is able to promote MMP-13 mRNA expression in rat HSCs and the JNK and p38 MAPK pathways were involved in this process. In summary, IL-1β-induced MMP-13 mRNA expression is possibly mediated by cytoplasmic JNK and p38 MAPK pathways, and they play a distinct role in this process. Thus, the JNK and p38 MAPK pathway co-operatively mediate MMP-13 mRNA expression in rat HSCs.
AuthorsNing Tang, Ya-Ping Zhang, Wang Ying, Xi-Xian Yao
JournalMolecular medicine reports (Mol Med Rep) Vol. 8 Issue 6 Pg. 1861-5 (Dec 2013) ISSN: 1791-3004 [Electronic] Greece
PMID24126863 (Publication Type: Journal Article)
Chemical References
  • Anthracenes
  • Imidazoles
  • Interleukin-1beta
  • Pyridines
  • RNA, Messenger
  • SB 203580
  • anthra(1,9-cd)pyrazol-6(2H)-one
  • JNK Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • Matrix Metalloproteinase 13
  • Animals
  • Anthracenes (pharmacology)
  • Cell Line
  • Gene Expression Regulation, Enzymologic (drug effects)
  • Hepatic Stellate Cells (drug effects, enzymology)
  • Imidazoles (pharmacology)
  • Interleukin-1beta (pharmacology)
  • JNK Mitogen-Activated Protein Kinases (metabolism)
  • MAP Kinase Signaling System (drug effects)
  • Matrix Metalloproteinase 13 (genetics, metabolism)
  • Models, Biological
  • Pyridines (pharmacology)
  • RNA, Messenger (genetics, metabolism)
  • Rats
  • Time Factors
  • Up-Regulation (drug effects)
  • p38 Mitogen-Activated Protein Kinases (metabolism)

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