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Vol.61 (2015) >

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タイトル: Membrane type 1-matrix metalloproteinase (MT1-MMP) identified as a multifunctional regulator of vascular responses
著者: Ohkawara, Hiroshi
Ikeda, Kazuhiko
Ogawa, Kazuei
Takeishi, Yasuchika
学内所属: 循環器・血液内科学講座
誌名/書名: Fukushima Journal of Medical Science
巻: 61
号: 2
開始ページ: 91
終了ページ: 100
発行日: 2015年
抄録: 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.
出版者: The Fukushima Society of Medical Science
出版者(異表記): 福島医学会
本文の言語: eng
このページのURI: http://ir.fmu.ac.jp/dspace/handle/123456789/487
本文URL: http://ir.fmu.ac.jp/dspace/bitstream/123456789/487/1/FksmJMedSci_61_p91.pdf
ISSN: 0016-2590
2185-4610
DOI: 10.5387/fms.2015-15
PubMed番号: 26370683
関連ページ: http://doi.org/10.5387/fms.2015-15
権利情報: © 2015 The Fukushima Society of Medical Science
出現コレクション:Vol.61 (2015)

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FksmJMedSci_61_p91.pdf1.42 MBAdobe PDFダウンロード

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