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

Authors

  • Yi-Chang Cheng
    • Emergency DepartmentTaichung Veterans General Hospital
  • Li-Mien Chen
    • Division of Medical Technology, Department of Internal MedicineArmed-Force Taichung General Hospital
  • Mu-Hsin Chang
    • Division of CardiologyArmed-Force Taichung General Hospital
  • Wei-Kung Chen
    • Emergency DepartmentChina Medical University Hospital
  • Fuu-Jen Tsai
    • Department of PediatricsMedical Research and Medical Genetics, China Medical University
  • Chang-Hai Tsai
    • Department of Healthcare AdministrationAsia University
  • Tung-Yuan Lai
    • Graduate Institute of Chinese Medical ScienceChina Medical University
  • Wei-Wen Kuo
    • Department of Biological Science and TechnologyChina Medical University
  • Chih-Yang Huang
    • Graduate Institute of Chinese Medical ScienceChina Medical University
    • Institute of Basic Medical ScienceChina Medical University
    • Department of Health and Nutrition BiotechnologyAsia University
    • Graduate Institute of Chinese Medical ScienceChina Medical University
Article

DOI: 10.1007/s11010-008-0016-y

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

Keywords

LipopolysaccharideMyocardial celluPAMMPsERK1/2 signaling pathway

Abbreviations

LPS

Lipopolysacchride

TLR

Toll-like receptor

ERK

Extracellular signal regulated kinase

p38 MAPK

p38 Mitogen-activated protein kinase

JNK

c-Jun N-terminal kinase

NF-κB

Nuclear factor κ B

uPA

Urokinase plasminogen activator

tPA

Tissue plasminogen activator

MMP

Matrix metallopeptidase

TIMP

Tissue inhibitor of metalloproteinases

CsA

Cyclosporine A

DMEM

Dulbecco’s modified Eagle’s medium

GAPDH

Glyceraldehyde-3-phosphate dehydrogenase

PBS

Phosphate-buffered saline

QNZ

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

ECM

Extracellular matrix

Copyright information

© Springer Science+Business Media, LLC. 2009