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Microarray analysis reveals the role of matrix metalloproteinases in mouse experimental autoimmune myocarditis induced by cardiac myosin peptides

Cellular & Molecular Biology Letters volume 12, pages 176–191 (2007)Cite this article

Abstract

Autoimmune myocarditis develops after the presentation of heart-specific antigens to autoaggressive CD4+ T cells and after inflammation has infiltrated the tissues. To shed light on global changes in the gene expression of autoimmune myocarditis and to gain further insight into the molecular mechanisms underlying the genesis of myocarditis, we conducted a comprehensive microarray analysis of mRNA using an experimental mouse autoimmune myocarditis model via immunization with α-myosin heavy chain-derived peptides. Of over 39,000 transcripts on a high density oligonucleotide microarray, 466 were under-expressed and 241 over-expressed by ≥ 1.5-fold compared with the controls in BALB/C mouse with autoimmune myocarditis. In this paper, we list the top 50 up-regulated genes related to the immune response. These altered genes encode for leukocyte-specific markers and receptors, the histocompatibility complex, cytokines/receptors, chemokines/receptors, adhesion molecules, components of the complement cascade, and signal transduction-related molecules. Interestingly, matrix metalloproteinases (MMPs) such as MMP-3 and MMP-9 were up-regulated, as further revealed by the reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry assays. This indicates that MMPs may act as major regulators of the cytokine profile. Together, these findings provide new insight into the molecular events associated with the mechanism of the autoimmune genesis of myocarditis.

Abbreviations

CFA:

complete Freund’s adjuvant

EAM:

experimental autoimmune myocarditis

ECM:

extracellular matrix

MCP:

monocyte chemoattractant protein

MHC:

major histocompatibility complex

MIP:

macrophage inflammatory protein

MMP:

matrix metalloproteinase

PBS:

phosphate buffered solution

RT-PCR:

reverse transcriptase-polymerase chain reaction

TIMPs:

tissue inhibitors of metalloproteinases

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Authors and Affiliations

  1. Department of Cardiology, Renmin Hospital of Wuhan University, 430060, Wuhan, P.R. China

    Qizhu Tang, Ji Huang, Ran Xiong, Difei Shen, Hui Wu, Zhouyan Bian & Xiaohong Wei

  2. Department of Cardiology, Fuwai Hospital and Cardiovascular Institute, Chinese Academy of Medical Science and Peking Union Medical College, 100037, Beijing, P.R. China

    Haiyan Qian

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  1. Qizhu Tang
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  2. Ji Huang
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  3. Haiyan Qian
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Correspondence to Qizhu Tang.

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Tang, Q., Huang, J., Qian, H. et al. Microarray analysis reveals the role of matrix metalloproteinases in mouse experimental autoimmune myocarditis induced by cardiac myosin peptides. Cell Mol Biol Lett 12, 176–191 (2007). https://doi.org/10.2478/s11658-007-0003-4

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Cellular & Molecular Biology Letters

ISSN: 1689-1392

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