Lipopolysaccharide upregulates uPA, MMP-2 and MMP-9 via ERK1/2 signaling in H9c2 cardiomyoblast cells

Yi Chang Cheng, Li Mien Chen, Mu Hsin Chang, Wei Kung Chen, Fuu Jen Tsai, Chang Hai Tsai, Tung Yuan Lai, Wei Wen Kuo, Chih Yang Huang, Chung Jung Liu

    Research output: Contribution to journalArticle

    37 Scopus citations

    Abstract

    Upregulation of urokinase plasminogen activator (uPA), tissue plasminogen activator (tPA), and matrix metallopeptidases (MMPs) is associated with the development of myocardial infarction (MI), dilated cardiomyopathy, cardiac fibrosis, and heart failure (HF). Evidences suggest that lipopolysaccharide (LPS) participates in the inflammatory response in the cardiovascular system; however, it is unknown if LPS is sufficient to upregulate expressions and/or activity of uPA, tPA, MMP-2, and MMP-9 in myocardial cells. In this study, we treated H9c2 cardiomyoblasts with LPS to explore whether LPS upregulates uPA, tPA, MMP-2, and MMP-9, and further to identify the precise molecular and cellular mechanisms behind this upregulatory responses. Here, we show that LPS challenge increased the protein levels of uPA, MMP-2 and MMP-9, and induced the activity of MMP-2 and MMP-9 in H9c2 cardiomyoblasts. However, LPS showed no effects on the expression of tissue inhibitor of metalloproteinase-1, -2, -3, and -4 (TIMP-1, -2, -3, and -4). After administration of inhibitors including U0126 (ERK1/2 inhibitor), SB203580 (p38 MAPK inhibitor), SP600125 (JNK1/2 inhibitor), CsA (calcineurin inhibitor), and QNZ (NFκB inhibitor), the LPS-upregulated expression and/or activity of uPA, MMP-2, and MMP-9 in H9c2 cardiomyoblasts are markedly inhibited only by ERK1/2 inhibitors, U0126. Collectively, these results suggest that LPS upregulates the expression and/or activity of uPA, MMP-2, and MMP-9 through ERK1/2 signaling pathway in H9c2 cardiomyoblasts. Our findings further provide a link between the LPS-induced cardiac dysfunction and the ERK1/2 signaling pathway that mediates the upregulation of uPA, MMP-2 and MMP-9.

    Original languageEnglish (US)
    Pages (from-to)15-23
    Number of pages9
    JournalMolecular and Cellular Biochemistry
    Volume325
    Issue number1-2
    DOIs
    StatePublished - Jan 29 2009

    Keywords

    • ERK1/2 signaling pathway
    • Lipopolysaccharide
    • MMPs
    • Myocardial cell
    • uPA

    ASJC Scopus subject areas

    • Molecular Biology
    • Clinical Biochemistry
    • Cell Biology

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  • Cite this

    Cheng, Y. C., Chen, L. M., Chang, M. H., Chen, W. K., Tsai, F. J., Tsai, C. H., Lai, T. Y., Kuo, W. W., Huang, C. Y., & Liu, C. J. (2009). Lipopolysaccharide upregulates uPA, MMP-2 and MMP-9 via ERK1/2 signaling in H9c2 cardiomyoblast cells. Molecular and Cellular Biochemistry, 325(1-2), 15-23. https://doi.org/10.1007/s11010-008-0016-y