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*

*此作品的通信作者

研究成果: 期刊稿件文章同行評審

27 引文 斯高帕斯(Scopus)

摘要

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.

原文英語
頁(從 - 到)241-246
頁數6
期刊Biochemical and Biophysical Research Communications
385
發行號2
DOIs
出版狀態已出版 - 24 07 2009

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