MEMBRANE TYPE 1-MATRIX METALLOPROTEINASE (MT1-MMP) IDENTIFIED AS A MULTIFUNCTIONAL REGULATOR OF VASCULAR RESPONSES
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- OHKAWARA HIROSHI
- Department of Cardiology and Hematology, Fukushima Medical University
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- IKEDA KAZUHIKO
- Department of Cardiology and Hematology, Fukushima Medical University Department of Blood Transfusion and Transplantation Immunology, Fukushima Medical University
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- OGAWA KAZUEI
- Department of Cardiology and Hematology, Fukushima Medical University
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- TAKEISHI YASUCHIKA
- Department of Cardiology and Hematology, Fukushima Medical University
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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 Ca2+ 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.
収録刊行物
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- 福島医学会
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福島医学会 61 (2), 91-100, 2015
福島医学会
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詳細情報 詳細情報について
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- CRID
- 1390282681281766272
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- NII論文ID
- 130005113561
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- NII書誌ID
- AA0065246X
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- ISSN
- 21854610
- 00162590
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- PubMed
- 26370683
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- IRDB
- Crossref
- PubMed
- CiNii Articles
- KAKEN
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- 抄録ライセンスフラグ
- 使用不可