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福島県立医科大学学術成果リポジトリ = Fukushima Medical University Repository >
福島医学会 = The Fukushima Society of Medical Science >
Fukushima Journal of Medical Science >
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
2185-4610 |
| 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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