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Vol.61 (2015) >

Please use this identifier to cite or link to this item: http://ir.fmu.ac.jp/dspace/handle/123456789/487

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Title: Membrane type 1-matrix metalloproteinase (MT1-MMP) identified as a multifunctional regulator of vascular responses
Authors: Ohkawara, Hiroshi
Ikeda, Kazuhiko
Ogawa, Kazuei
Takeishi, Yasuchika
Affiliation: 循環器・血液内科学講座
Source title: Fukushima Journal of Medical Science
Volume: 61
Issue: 2
Start page: 91
End page: 100
Issue Date: 2015
Abstract: Membrane type 1-matrix metalloproteinase (MT1-MMP) functions as a signaling molecules in addition to a transmembrane metalloprotease, which degrades interstitial collagens and extracellular matrix components. This review focuses on the multifunctional roles of MT1-MMP as a signaling molecule in vascular responses to pro-atherosclerotic stimuli in the pathogenesis of cardiovascular diseases. First, the lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1)-MT1-MMP signaling axis contributes to endothelial dysfunction, which is mediated via small GTP-binding protein RhoA and Rac1 activation. Second, MT1-MMP plays a crucial role in reactive oxygen species (ROS) generation through the activation of receptor for advanced glycation end products (AGEs) in smooth muscle cells, indicating that MT1-MMP may be a therapeutic target for diabetic vascular complications. Third, MT1-MMP is involved in RhoA/Rac1 activation and Ca^{2+} signaling in the mechanism of thrombin-stimulated endothelial dysfunction and oxidant stress. Fourth, the inhibition of the MT1-MMP/Akt signaling pathway may be an attractive strategy for treating endothelial disordered hemostasis in the development of vascular diseases linked to TNF-α-induced inflammation. Fifth, MT1-MMP through RAGE induced RhoA/Rac1 activation and tissue factor protein upregulation through NF-κB phosphorylation in endothelial cells stimulated by high-mobility group box-1, which plays a key role in the systemic inflammation. These findings suggest that the MT1-MMP-mediated signaling axis may be a promising target for treating atherosclerosis and subsequent cardiovascular diseases.
Publisher: The Fukushima Society of Medical Science
Publisher (Alternative foam): 福島医学会
language: eng
URI: http://ir.fmu.ac.jp/dspace/handle/123456789/487
Full text URL: http://ir.fmu.ac.jp/dspace/bitstream/123456789/487/1/FksmJMedSci_61_p91.pdf
ISSN: 0016-2590
DOI: 10.5387/fms.2015-15
PubMed ID: 26370683
Related Page: http://doi.org/10.5387/fms.2015-15
Rights: © 2015 The Fukushima Society of Medical Science
Appears in Collections:Vol.61 (2015)

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FksmJMedSci_61_p91.pdf1.42 MBAdobe PDFDownload

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