Mechanical stretch induces matrix metalloproteinase 1 production in human hepatic stellate cells

2004 ◽  
Vol 11 (3) ◽  
pp. 153-158 ◽  
Author(s):  
Takashi Goto ◽  
Ken-ichiro Mikami ◽  
Kouich Miura ◽  
Shigetoshi Ohshima ◽  
Kazuo Yoneyama ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Hepatic Stellate Cells ◽  
Stellate Cells ◽  
Mechanical Stretch ◽  
Matrix Metalloproteinase 1

Mechanical stretch induces matrix metalloproteinase 1 production in hepatic stellate cells

2001 ◽  
Vol 120 (5) ◽  
pp. A359 ◽  
Author(s):  
Takashi Goto ◽  
Ken-Ichiro Mikami ◽  
Kouithi Miura ◽  
Kazuo Yoneyama ◽  
Kunio Nakane ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Hepatic Stellate Cells ◽  
Stellate Cells ◽  
Mechanical Stretch ◽  
Matrix Metalloproteinase 1

Mechanical stretch induces matrix metalloproteinase 1 production in hepatic stellate cells

2001 ◽  
Vol 120 (5) ◽  
pp. A359-A359
Author(s):  
T GOTO ◽  
K MIKAMI ◽  
K MIURA ◽  
K YONEYAMA ◽  
K NAKANE ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Hepatic Stellate Cells ◽  
Stellate Cells ◽  
Mechanical Stretch ◽  
Matrix Metalloproteinase 1

Molecular Mechanisms of Matrix Metalloproteinase-1 Gene Expression in Hepatic Stellate Cells

2001 ◽  
pp. 336-339
Author(s):  
Shigenari Hozawa ◽  
Haruko Suzuki ◽  
Sachiko Kagawa ◽  
Ayako Higuchi ◽  
Tetsu Watanabe ◽  
...  
Keyword(s):  
Gene Expression ◽  
Matrix Metalloproteinase ◽  
Hepatic Stellate Cells ◽  
Molecular Mechanisms ◽  
Stellate Cells ◽  
Matrix Metalloproteinase 1

scholarly journals The CYP2E1 inhibitor DDC up-regulates MMP-1 expression in hepatic stellate cells via an ERK1/2- and Akt-dependent mechanism

2013 ◽  
Vol 33 (3) ◽  
Author(s):  
Tianhui Liu ◽  
Ping Wang ◽  
Min Cong ◽  
Youqing Xu ◽  
Jidong Jia ◽  
...  
Keyword(s):  
Enzyme Activity ◽  
Matrix Metalloproteinase ◽  
Hepatic Stellate Cells ◽  
Treatment Strategies ◽  
Stellate Cells ◽  
Collagen I ◽  
Akt Inhibitor ◽  
H2o2 Treatment ◽  
P38 Inhibitor ◽  
Matrix Metalloproteinase 1

DDC (diethyldithiocarbamate) could block collagen synthesis in HSC (hepatic stellate cells) through the inhibition of ROS (reactive oxygen species) derived from hepatocyte CYP2E1 (cytochrome P450 2E1). However, the effect of DDC on MMP-1 (matrix metalloproteinase-1), which is the main collagen degrading matrix metalloproteinase, has not been reported. In co-culture experiments, we found that DDC significantly enhanced MMP-1 expression in human HSC (LX-2) that were cultured with hepatocyte C3A cells either expressing or not expressing CYP2E1. The levels of both proenzyme and active MMP-1 enzyme were up-regulated in LX-2 cells, accompanied by elevated enzyme activity of MMP-1 and decreased collagen I, in both LX-2 cells and the culture medium. H2O2 treatment abrogated DDC-induced MMP-1 up-regulation and collagen I decrease, while catalase treatment slightly up-regulated MMP-1 expression. These data suggested that the decrease in ROS by DDC was partially responsible for the MMP-1 up-regulation. ERK1/2 (extracellular signal-regulated kinase 1/2), Akt (protein kinase B) and p38 were significantly activated by DDC. The ERK1/2 inhibitor (U0126) and Akt inhibitor (T3830) abrogated the DDC-induced MMP-1 up-regulation. In addition, a p38 inhibitor (SB203580) improved MMP-1 up-regulation through the stimulation of ERK1/2. Our data indicate that DDC significantly up-regulates the expression of MMP-1 in LX-2 cells which results in greater MMP-1 enzyme activity and decreased collagen I. The enhancement of MMP-1 expression by DDC was associated with H2O2 inhibition and coordinated regulation by the ERK1/2 and Akt pathways. These data provide some new insights into treatment strategies for hepatic fibrosis.

scholarly journals Matrix metalloproteinase-1 induction by diethyldithiocarbamate is regulated via Akt and ERK/miR222/ETS-1 pathways in hepatic stellate cells

2016 ◽  
Vol 36 (4) ◽  
Author(s):  
Tianhui Liu ◽  
Ping Wang ◽  
Min Cong ◽  
Dong Zhang ◽  
Lin Liu ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Hepatic Stellate Cells ◽  
Molecular Mechanisms ◽  
Stellate Cells ◽  
Transcriptional Factor ◽  
Signalling Pathways ◽  
Akt Inhibitor ◽  
Matrix Metalloproteinase 1 ◽  
Prevention And Treatment ◽  
Important Regulator

Matrix metalloproteinase-1 (MMP-1) plays an important role in fibrolysis by degrading excessively deposited collagen I and III. We previously demonstrated that diethyldithiocarbamate (DDC) up-regulates MMP-1 in hepatic stellate cells via the ERK1/2 and Akt signalling pathways. In the current study, we attempted to further explore the molecular mechanisms involved in the regulation of MMP-1. We treated a co-cultured system that included hepatocytes (C3A) and hepatic stellate cells (LX-2) with DDC. The data revealed that the transcriptional factor ETS-1, which is an important regulator of MMP-1, was up-regulated in LX-2 cells following DDC treatment. Furthermore, the up-regulation of MMP-1 by DDC has been abrogated through employing si-ETS-1 to block expression of ETS-1. We found that DDC significantly inhibited the expression of miR-222 in LX-2 cells. We transfected miR-222 mimic into LX-2 cells and then co-cultured the cells with C3A. The up-regulation of ETS-1 and MMP-1 in LX-2 cells treated with DDC were inhibited after miR-222 mimic transfection. These data indicate that DDC up-regulated MMP-1 in LX-2 cells through the miR-222/ETS-1 pathway. Finally, we treated the co-cultured system with an Akt inhibitor (T3830) and an ERK1/2 inhibitor (U0126). Both T3830 and U0126 blocked the suppression of miR-222 by DDC in LX-2. Collectively, these data indicate that DDC up-regulated MMP-1 in LX-2 cells through the Akt and ERK/miR-222/ETS-1 pathways. Our study provides experimental data that will aid the control of the process of fibrolysis in liver fibrosis prevention and treatment.

Active matrix metalloproteinase-2 promotes apoptosis of hepatic stellate cells via the cleavage of cellular N-cadherin

2009 ◽  
Vol 29 (7) ◽  
pp. 966-978 ◽  
Author(s):  
Stephen N. Hartland ◽  
Frank Murphy ◽  
Rebecca L. Aucott ◽  
Armand Abergel ◽  
Xiaoying Zhou ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Hepatic Stellate Cells ◽  
Stellate Cells ◽  
Matrix Metalloproteinase 2 ◽  
Active Matrix
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