Upregulation of fibroblast growth factor (FGF), 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 FGF-2, uPA, tPA, MMP-2 and MMP-9 in cardiac fibroblasts. In the present study, we treated primary cardiac fibroblasts with LPS to explore whether LPS upregulates FGF-2, uPA, tPA, MMP-2, MMP-9 and cellular migration, and further to identify the precise molecular and cellular mechanisms behind these upregulatory responses. Here we show that LPS challenge increased the protein levels of FGF-2, uPA, MMP-2 and MMP-9, and induced the activity of MMP-2 and MMP-9 in cardiac fibroblasts. After administration of inhibitors including U0126 (ERK1/2 inhibitor), SB203580 (p38 MAPK inhibitor), SP600125 (JNK1/2 inhibitor), CsA (calcineurin inhibitor) and QNZ (NFkB inhibitor), the LPS-upregulated expression and/or activity of FGF-2, uPA, MMP-2 and MMP-9 in cardiac fibroblasts is markedly inhibited only by ERK1/2 inhibitors, U0126. Collectively, these results suggest that LPS upregulates the expression and/or activity of FGF-2, uPA, MMP-2 and MMP-9, and the subsequent cell migration through ERK1/2 signalling pathway in primary cardiac fibroblasts. Our findings further provide a link between the LPS-induced cardiac dysfunction and the ERK1/2 signalling pathway that mediates the upregulation of FGF-2, uPA, MMP-2, MMP-9 and cellular migration in Primary Cardiac Fibroblasts.
- urokinase plasminogen activator
- tissue plasminogen activator
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