Oncostatin M, an interleukin-6 family cytokine, upregulates matrix metalloproteinase-9 through the mitogen-activated protein kinase kinase-extracellular signal-regulated kinase pathway in cultured smooth muscle cells

Tsuyoshi Nagata, Hisashi Kai, Rei Shibata, Mitsuhisa Koga, Akihiko Yoshimura, Tsutomu Imaizumi

Research output: Contribution to journalArticlepeer-review

31 Citations (Scopus)

Abstract

Objectives - Matrix metalloproteinase (MMP)-9 is implicated in extracellular matrix (ECM) degradation of atherosclerotic lesions. Oncostatin M (OSM) regulates ECM metabolism in various kinds of cells. Thus, we sought to investigate whether OSM regulates MMP-9 expression in cultured rat aortic smooth muscle cells (SMCs) and, if so, to determine the signaling pathway for MMP-9 induction by OSM. Methods and Results - Competitive reverse transcriptase polymerase chain reaction showed that OSM upregulated MMP-9 mRNA expression, peaking at 4 hours and returning to unstimulated levels by 24 hours. Gelatin zymography revealed that MMP-9 activity was increased in the conditioned medium after the 24-hour OSM treatment. Immunoblot analysis demonstrated that OSM transiently induced extracellular signal-regulated kinase (ERK)1/2 and STAT3 phosphorylations with a peak at 15 and 5 minutes, respectively. A MEK1 inhibitor, PD98059, not only blocked ERK1/2 phosphorylation but also abolished the OSM-induced MMP-9 upregulation, whereas the MMP-9 induction was not affected by overexpressing dominant-negative STAT3. In addition, OSM slightly upregulated MMP-2 and downregulated tissue inhibitors of MMP-1 and -3 through different mechanisms from that in case of MMP-9. Conclusions - OSM upregulates MMP-9 expression in SMCs through the MEK-ERK but not STAT3 pathway.

Original languageEnglish
Pages (from-to)588-593
Number of pages6
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume23
Issue number4
DOIs
Publication statusPublished - 2003 Apr 1
Externally publishedYes

Keywords

  • Matrix metalloproteinase
  • Muscle
  • Oncostatin M
  • Signal transduction
  • Smooth

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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