Molecular and Cellular Biochemistry

, Volume 325, Issue 1, pp 15-23

First online:

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

  • Yi-Chang ChengAffiliated withEmergency Department, Taichung Veterans General Hospital
  • , Li-Mien ChenAffiliated withDivision of Medical Technology, Department of Internal Medicine, Armed-Force Taichung General Hospital
  • , Mu-Hsin ChangAffiliated withDivision of Cardiology, Armed-Force Taichung General Hospital
  • , Wei-Kung ChenAffiliated withEmergency Department, China Medical University Hospital
  • , Fuu-Jen TsaiAffiliated withDepartment of Pediatrics, Medical Research and Medical Genetics, China Medical University
  • , Chang-Hai TsaiAffiliated withDepartment of Healthcare Administration, Asia University
  • , Tung-Yuan LaiAffiliated withGraduate Institute of Chinese Medical Science, China Medical University
  • , Wei-Wen KuoAffiliated withDepartment of Biological Science and Technology, China Medical University
  • , Chih-Yang HuangAffiliated withGraduate Institute of Chinese Medical Science, China Medical UniversityInstitute of Basic Medical Science, China Medical UniversityDepartment of Health and Nutrition Biotechnology, Asia University
    • , Chung-Jung LiuAffiliated withGraduate Institute of Chinese Medical Science, China Medical University Email author 

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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.


Lipopolysaccharide Myocardial cell uPA MMPs ERK1/2 signaling pathway