TGF-β dependent regulation of oxygen radicals during transdifferentiation of activated hepatic stellate cells to myofibroblastoid cells
| Autor: | Miguel M. Murillo, Wolfgang Mikulits, Irene Carmona-Cuenca, Heidemarie Huber, Verena Proell, Isabel Fabregat |
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| Přispěvatelé: | Universitat de Barcelona |
| Rok vydání: | 2007 |
| Předmět: |
medicine.medical_specialty
medicine.disease_cause Liver cells Cèl·lules hepàtiques Superoxide dismutase chemistry.chemical_compound Downregulation and upregulation Internal medicine medicine Liver diseases chemistry.chemical_classification Reactive oxygen species NADPH oxidase Hepatology biology business.industry Research Malalties del fetge Transdifferentiation Glutathione Cell biology Endocrinology chemistry biology.protein Hepatic stellate cell business Oxidative stress |
| Zdroj: | Dipòsit Digital de la UB Universidad de Barcelona Recercat. Dipósit de la Recerca de Catalunya instname Comparative Hepatology |
| ISSN: | 1476-5926 |
| DOI: | 10.1186/1476-5926-6-1 |
| Popis: | Background The activation of hepatic stellate cells (HSCs) plays a pivotal role during liver injury because the resulting myofibroblasts (MFBs) are mainly responsible for connective tissue re-assembly. MFBs represent therefore cellular targets for anti-fibrotic therapy. In this study, we employed activated HSCs, termed M1-4HSCs, whose transdifferentiation to myofibroblastoid cells (named M-HTs) depends on transforming growth factor (TGF)-β. We analyzed the oxidative stress induced by TGF-β and examined cellular defense mechanisms upon transdifferentiation of HSCs to M-HTs. Results We found reactive oxygen species (ROS) significantly upregulated in M1-4HSCs within 72 hours of TGF-β administration. In contrast, M-HTs harbored lower intracellular ROS content than M1-4HSCs, despite of elevated NADPH oxidase activity. These observations indicated an upregulation of cellular defense mechanisms in order to protect cells from harmful consequences caused by oxidative stress. In line with this hypothesis, superoxide dismutase activation provided the resistance to augmented radical production in M-HTs, and glutathione rather than catalase was responsible for intracellular hydrogen peroxide removal. Finally, the TGF-β/NADPH oxidase mediated ROS production correlated with the upregulation of AP-1 as well as platelet-derived growth factor receptor subunits, which points to important contributions in establishing antioxidant defense. Conclusion The data provide evidence that TGF-β induces NADPH oxidase activity which causes radical production upon the transdifferentiation of activated HSCs to M-HTs. Myofibroblastoid cells are equipped with high levels of superoxide dismutase activity as well as glutathione to counterbalance NADPH oxidase dependent oxidative stress and to avoid cellular damage. |
| Databáze: | OpenAIRE |
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