ArticleBioscience reports2013
The CYP2E1 inhibitor DDC up-regulates MMP-1 expression in hepatic stellate cells via an ERK1/2- and Akt-dependent mechanism.
Article in Bioscience reports, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.
- Relationship of ALDH2 rs671 and CYP2E1 rs2031920 with hepatocellular carcinoma susceptibility in East Asians: a meta-analysis.World journal of surgical oncology · 2020Pooled it
- Resolving fibrosis by stimulating HSC-dependent extracellular matrix degradation.Science translational medicine · 2025Article
- The role of hepatic sinusoidal microenvironment in NASH: pathogenesis, animal models, and therapeutic prospects.Frontiers in pharmacology · 2025Review
- Activin A plays an essential role in migration and proliferation of hepatic stellate cells via Smad3 and calcium signaling.Scientific reports · 2024Article
- Peridroplet mitochondria are associated with the severity of MASLD and the prevention of MASLD by diethyldithiocarbamate.Journal of lipid research · 2024Article
- Disulfiram inhibits liver fibrosis in rats by suppressing hepatic stellate cell activation and viability.BMC pharmacology & toxicology · 2022Article
- A Spatiotemporal Characterisation of Redox Molecules in Planarians, with a Focus on the Role of Glutathione during Regeneration.Biomolecules · 2021Article
- Diethyldithiocarbamate, an anti-abuse drug, alleviates steatohepatitis and fibrosis in rodents through modulating lipid metabolism and oxidative stress.British journal of pharmacology · 2018Article
- Matrix metalloproteinase-1 induction by diethyldithiocarbamate is regulated via Akt and ERK/miR222/ETS-1 pathways in hepatic stellate cells.Bioscience reports · 2016Article
- Hepatitis C Virus NS5A Protein Triggers Oxidative Stress by Inducing NADPH Oxidases 1 and 4 and Cytochrome P450 2E1.Oxidative medicine and cellular longevity · 2016Article
- HCV core protein uses multiple mechanisms to induce oxidative stress in human hepatoma Huh7 cells.Viruses · 2015Article
- The role of cyclooxygenase-2, interleukin-1β and fibroblast growth factor-2 in the activation of matrix metalloproteinase-1 in sheared-chondrocytes and articular cartilage.Scientific reports · 2015Article
- Cellular and molecular mechanisms in the pathogenesis of liver fibrosis: An update.World journal of gastroenterology · 2014Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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