Molecular and Cellular Biochemistry

, Volume 325, Issue 1, pp 15–23

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

DOI: 10.1007/s11010-008-0016-y

Cite this article as:
Cheng, YC., Chen, LM., Chang, MH. et al. Mol Cell Biochem (2009) 325: 15. doi:10.1007/s11010-008-0016-y


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.


LipopolysaccharideMyocardial celluPAMMPsERK1/2 signaling pathway





Toll-like receptor


Extracellular signal regulated kinase

p38 MAPK

p38 Mitogen-activated protein kinase


c-Jun N-terminal kinase


Nuclear factor κ B


Urokinase plasminogen activator


Tissue plasminogen activator


Matrix metallopeptidase


Tissue inhibitor of metalloproteinases


Cyclosporine A


Dulbecco’s modified Eagle’s medium


Glyceraldehyde-3-phosphate dehydrogenase


Phosphate-buffered saline


6-Amino-4-(4-phenoxyphenylethylamino) quinazoline


Extracellular matrix

Copyright information

© Springer Science+Business Media, LLC. 2009

Authors and Affiliations

  • Yi-Chang Cheng
    • 1
  • Li-Mien Chen
    • 2
  • Mu-Hsin Chang
    • 3
  • Wei-Kung Chen
    • 4
  • Fuu-Jen Tsai
    • 5
  • Chang-Hai Tsai
    • 6
  • Tung-Yuan Lai
    • 7
  • Wei-Wen Kuo
    • 8
  • Chih-Yang Huang
    • 7
    • 9
    • 10
  • Chung-Jung Liu
    • 7
  1. 1.Emergency DepartmentTaichung Veterans General HospitalTaichungTaiwan
  2. 2.Division of Medical Technology, Department of Internal MedicineArmed-Force Taichung General HospitalTaichungTaiwan
  3. 3.Division of CardiologyArmed-Force Taichung General HospitalTaichungTaiwan
  4. 4.Emergency DepartmentChina Medical University HospitalTaichungTaiwan
  5. 5.Department of PediatricsMedical Research and Medical Genetics, China Medical UniversityTaichungTaiwan
  6. 6.Department of Healthcare AdministrationAsia UniversityTaichungTaiwan
  7. 7.Graduate Institute of Chinese Medical ScienceChina Medical UniversityTaichungTaiwan
  8. 8.Department of Biological Science and TechnologyChina Medical UniversityTaichungTaiwan
  9. 9.Institute of Basic Medical ScienceChina Medical UniversityTaichungTaiwan
  10. 10.Department of Health and Nutrition BiotechnologyAsia UniversityTaichungTaiwan