ArticleInternational journal of molecular sciences2011
Reactive oxygen species released from hypoxic hepatocytes regulates MMP-2 expression in hepatic stellate cells.
Article in International journal of molecular sciences, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 46 citations in OpenAlex.
- The intersection of liver cirrhosis and pulmonary fibrosis.Journal of translational medicine · 2025Review
- Investigation of the effects of white tea on liver fibrosis: An experimental animal model.Food science & nutrition · 2024Article
- From liver fibrosis to hepatocarcinogenesis: Role of excessive liver HBioactive materials · 2023Article
- Unboxing the molecular modalities of mutagens in cancer.Environmental science and pollution research international · 2022Review
- Oxidative stress-mediated mitochondrial fission promotes hepatic stellate cell activation via stimulating oxidative phosphorylation.Cell death & disease · 2022Article
- Mesenchymal Stem Cells Influence Activation of Hepatic Stellate Cells, and Constitute a Promising Therapy for Liver Fibrosis.Biomedicines · 2021Review
- Extra virgin olive oil improved body weight and insulin sensitivity in high fat diet-induced obese LDLr-/-.Leiden mice without attenuation of steatohepatitis.Scientific reports · 2021Article
- Palmitate and pyruvate carbon flux in response to choline and methionine in bovine neonatal hepatocytes.Scientific reports · 2020Article
- Elucidating Potential Profibrotic Mechanisms of Emerging Biomarkers for Early Prognosis of Hepatic Fibrosis.International journal of molecular sciences · 2020Review
- Food components with antifibrotic activity and implications in prevention of liver disease.The Journal of nutritional biochemistry · 2018Review
- Polymorphisms in matrix metalloproteinases 2, 3, and 8 increase recurrence and mortality risk by regulating enzyme activity in gastric adenocarcinoma.Oncotarget · 2017Article
- Proteomic and transcriptomic studies of HBV-associated liver fibrosis of an AAV-HBV-infected mouse model.BMC genomics · 2017Article
- MMP-2 and 9 in Chronic Kidney Disease.International journal of molecular sciences · 2017Review
- Protective effect of rosuvastatin treatment by regulating oxidized low-density lipoprotein expression in a rat model of liver fibrosis.Biomedical reports · 2016Article
- Insights into the Role and Interdependence of Oxidative Stress and Inflammation in Liver Diseases.Oxidative medicine and cellular longevity · 2016Review
- The Interplay of Reactive Oxygen Species, Hypoxia, Inflammation, and Sirtuins in Cancer Initiation and Progression.Oxidative medicine and cellular longevity · 2016Review
- Inhibition of liver fibrosis using vitamin A-coupled liposomes to deliver matrix metalloproteinase-2 siRNA in vitro.Molecular medicine reports · 2015Article
- Obstructive sleep apnea is an important predictor of hepatic fibrosis in patients with nonalcoholic fatty liver disease in a tertiary care center.Hepatology international · 2015Article
- OSAS-related inflammatory mechanisms of liver injury in nonalcoholic fatty liver disease.Mediators of inflammation · 2015Review
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hypoxia is a common environmental stress factor and is associated with fibrogenesis. Matrix metalloproteinase-2 (MMP-2), produced by hepatic stellate cells (HSCs), plays an important role in liver fibrogenesis. However, inconsistent results have been reported on the impact of hypoxia on MMP-2 expression and activity in HSCs. We speculated that cell-cell interaction is involved in the regulation of MMP-2 expression and activity at low oxygen level in vivo. Therefore, in this report we investigated the mechanism by which hypoxic hepatocytes regulates MMP-2 expression in HSCs. Our results showed that the conditioned medium from hypoxia-treated rat hepatocytes strongly induced the expression of MMP-2 mRNA and protein in rat HSC-T6 cells. Reduced glutathione neutralized ROS released from hypoxic hepatocytes, leading to reduced MMP-2 expression in HSC-T6 cells. In addition, phospho-IκB-α protein level was increased in HSC-T6 cells treated with hypoxia conditioned medium, and NF-κB signaling inhibitor inhibited MMP-2 expression in HSC-T6 cells. Taken together, our data suggest that ROS is an important factor released by hypoxic hepatocytes to regulate MMP-2 expression in HSCs, and NF-κB signaling is crucially involved in ROS-induced MMP-2 expression in HSCs. Our findings suggest that strategies aimed at antagonizing the generation of ROS in hypoxic hepatocytes and inhibiting NF-κB signaling in HSCs may represent novel therapeutic options for liver fibrosis.
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