Thrombin regulates matrix metalloproteinase-9 expression in human monocytes

Chi Jen Chang, Lung An Hsu, Yu Hsein Ko, Pei Ling Chen, Yi Ting Chuang, Chun Yen Lin, Chang Hui Liao, Jong Hwei S. Pang*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

27 Scopus citations

Abstract

We investigated whether thrombin, the final activator of coagulation cascade, regulates expression of matrix metalloproteinases (MMP)-9 in human monocytes. We show that thrombin stimulation induced MMP-9 secretion of monocytes dose- and time-dependently as revealed by gelatin zymography. Real-time RT-PCR and Western blot analysis demonstrated that thrombin up-regulated mRNA and protein levels of MMP-9. Pre-incubation with anti-protease-activated receptor (PAR)-1 or anti-PAR-3 antibody partially inhibited the thrombin-induced MMP-9 secretion. Simultaneous incubation with both showed synergistic effect, indicating the involvement of both receptors in this thrombin effect. BAPTA, a Ca2+ chelator, abolished the thrombin-induced MMP-9 secretion, indicating the requirement of Ca2+ mobilization in this process. Inhibition of thrombin-induced MMP-9 secretion by either MEK inhibitor or p38 kinase inhibitor revealed that the thrombin effect was mediated by both ERK1/2 and p38 pathways. The activation of NFκB by thrombin as demonstrated by electromobility shift assay was also shown to be critical to the thrombin-induced MMP-9 up-regulation.

Original languageEnglish
Pages (from-to)241-246
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume385
Issue number2
DOIs
StatePublished - 24 07 2009

Keywords

  • Matrix metalloproteinase
  • Monocytes
  • Thrombin

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