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Cardiotrophin-1 Induces Matrix Metalloproteinase-1 in Human Aortic Endothelial Cells

Rupture of an atherosclerotic plaque is a key event in the development of cardiovascular disorders, in which matrix metalloproteinase-1 (MMP-1) plays a crucial role by degradation of extracellular matrix resulting in plaque instability. Cardiotrophin-1 (CT-1), a member of interleukin-6-type proinfla...

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Autores principales: Tokito, Akinori, Jougasaki, Michihisa, Ichiki, Tomoko, Hamasaki, Shuichi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3720803/
https://www.ncbi.nlm.nih.gov/pubmed/23935888
http://dx.doi.org/10.1371/journal.pone.0068801
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author Tokito, Akinori
Jougasaki, Michihisa
Ichiki, Tomoko
Hamasaki, Shuichi
author_facet Tokito, Akinori
Jougasaki, Michihisa
Ichiki, Tomoko
Hamasaki, Shuichi
author_sort Tokito, Akinori
collection PubMed
description Rupture of an atherosclerotic plaque is a key event in the development of cardiovascular disorders, in which matrix metalloproteinase-1 (MMP-1) plays a crucial role by degradation of extracellular matrix resulting in plaque instability. Cardiotrophin-1 (CT-1), a member of interleukin-6-type proinflammatory cytokines, has potent cardiovascular actions and is highly expressed in vascular endothelium, however its role in atherosclerosis has not been fully elucidated to date. The present study was designed to investigate whether CT-1 induces MMP-1 in human aortic endothelial cells (HAECs). Ribonuclease protection assay demonstrated that MMP-1 gene level in HAECs was enhanced by the treatment of CT-1 in a dose- and time-dependent manner. Immunocytochemical staining, Western immunoblot analysis and enzyme-linked immunosorbent assay revealed that CT-1 augmented MMP-1 protein synthesis and secretion. MMP-1 activity assay revealed that MMP-1 present in the supernatant of HAECs was exclusively precursor form. Casein zymography disclosed proteolytic activity in the supernatant of HAECs, which was enhanced by CT-1 treatment. Furthermore, pharmacological inhibitor study indicated the important roles of extracellular signal-regulated kinase (ERK) 1/2, p38 mitogen-activated protein (MAP) kinase, c-Jun N-terminal kinase (JNK) and Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling pathways in mediating CT-1-induced MMP-1 gene and protein expression. These data reveal for the first time that CT-1 induces the proteolytic potential in HAECs by upregulating MMP-1 expression through ERK1/2, p38 MAP kinase, JNK and JAK/STAT pathways, and suggest that CT-1 may play an important role in the pathophysiology of atherosclerosis and plaque instability.
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spelling pubmed-37208032013-08-09 Cardiotrophin-1 Induces Matrix Metalloproteinase-1 in Human Aortic Endothelial Cells Tokito, Akinori Jougasaki, Michihisa Ichiki, Tomoko Hamasaki, Shuichi PLoS One Research Article Rupture of an atherosclerotic plaque is a key event in the development of cardiovascular disorders, in which matrix metalloproteinase-1 (MMP-1) plays a crucial role by degradation of extracellular matrix resulting in plaque instability. Cardiotrophin-1 (CT-1), a member of interleukin-6-type proinflammatory cytokines, has potent cardiovascular actions and is highly expressed in vascular endothelium, however its role in atherosclerosis has not been fully elucidated to date. The present study was designed to investigate whether CT-1 induces MMP-1 in human aortic endothelial cells (HAECs). Ribonuclease protection assay demonstrated that MMP-1 gene level in HAECs was enhanced by the treatment of CT-1 in a dose- and time-dependent manner. Immunocytochemical staining, Western immunoblot analysis and enzyme-linked immunosorbent assay revealed that CT-1 augmented MMP-1 protein synthesis and secretion. MMP-1 activity assay revealed that MMP-1 present in the supernatant of HAECs was exclusively precursor form. Casein zymography disclosed proteolytic activity in the supernatant of HAECs, which was enhanced by CT-1 treatment. Furthermore, pharmacological inhibitor study indicated the important roles of extracellular signal-regulated kinase (ERK) 1/2, p38 mitogen-activated protein (MAP) kinase, c-Jun N-terminal kinase (JNK) and Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling pathways in mediating CT-1-induced MMP-1 gene and protein expression. These data reveal for the first time that CT-1 induces the proteolytic potential in HAECs by upregulating MMP-1 expression through ERK1/2, p38 MAP kinase, JNK and JAK/STAT pathways, and suggest that CT-1 may play an important role in the pathophysiology of atherosclerosis and plaque instability. Public Library of Science 2013-07-23 /pmc/articles/PMC3720803/ /pubmed/23935888 http://dx.doi.org/10.1371/journal.pone.0068801 Text en © 2013 Tokito et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Tokito, Akinori
Jougasaki, Michihisa
Ichiki, Tomoko
Hamasaki, Shuichi
Cardiotrophin-1 Induces Matrix Metalloproteinase-1 in Human Aortic Endothelial Cells
title Cardiotrophin-1 Induces Matrix Metalloproteinase-1 in Human Aortic Endothelial Cells
title_full Cardiotrophin-1 Induces Matrix Metalloproteinase-1 in Human Aortic Endothelial Cells
title_fullStr Cardiotrophin-1 Induces Matrix Metalloproteinase-1 in Human Aortic Endothelial Cells
title_full_unstemmed Cardiotrophin-1 Induces Matrix Metalloproteinase-1 in Human Aortic Endothelial Cells
title_short Cardiotrophin-1 Induces Matrix Metalloproteinase-1 in Human Aortic Endothelial Cells
title_sort cardiotrophin-1 induces matrix metalloproteinase-1 in human aortic endothelial cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3720803/
https://www.ncbi.nlm.nih.gov/pubmed/23935888
http://dx.doi.org/10.1371/journal.pone.0068801
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