Article ; Online: Oncostatin M, A Profibrogenic Mediator Overexpressed in Non-Alcoholic Fatty Liver Disease, Stimulates Migration of Hepatic Myofibroblasts.
2019 Volume 9, Issue 1
Abstract: Background: Hepatic myofibroblasts (MFs) can originate from hepatic stellate cells, portal fibroblasts, or bone marrow-derived mesenchymal stem cells and can migrate towards the site of injury by aligning with nascent and established fibrotic septa in ... ...
| Abstract | Background: Hepatic myofibroblasts (MFs) can originate from hepatic stellate cells, portal fibroblasts, or bone marrow-derived mesenchymal stem cells and can migrate towards the site of injury by aligning with nascent and established fibrotic septa in response to several mediators. Oncostatin M (OSM) is known to orchestrate hypoxia-modulated hepatic processes involving the hypoxia-inducible factor 1 (HIF-1). Methods: In vivo and in vitro experiments were performed to analyze the expression of OSM and OSM-receptor (OSMR) in three murine models of non-alcoholic-fatty liver disease (NAFLD) and -steatohepatitis (NASH) and in human NASH patients as well as the action of OSM on phenotypic responses of human MFs. Results: Hepatic OSM and OSMR levels were overexpressed in three murine NASH models and in NASH patients. OSM stimulates migration in human MFs by involving early intracellular ROS generation and activation of Ras/Erk, JNK1/2, PI3K/Akt as well as STAT1/STAT3 pathways and HIF-1α. OSM-dependent migration relies on a biphasic mechanism requiring early intracellular generation of reactive oxygen species (ROS) and late HIF1-dependent expression and release of VEGF. Conclusion: OSM is overexpressed in experimental and human progressive NAFLD and can act as a profibrogenic factor by directly stimulating migration of hepatic MFs. |
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| MeSH term(s) | Animals ; Cell Line ; Cell Movement/drug effects ; Disease Models, Animal ; Humans ; Hypoxia-Inducible Factor 1/metabolism ; Mice ; Myofibroblasts/cytology ; Myofibroblasts/metabolism ; Non-alcoholic Fatty Liver Disease/genetics ; Non-alcoholic Fatty Liver Disease/metabolism ; Oncostatin M/genetics ; Oncostatin M/metabolism ; Oncostatin M Receptor beta Subunit/genetics ; Oncostatin M Receptor beta Subunit/metabolism ; Reactive Oxygen Species/metabolism ; Signal Transduction ; Up-Regulation ; Vascular Endothelial Growth Factor A/metabolism |
| Chemical Substances | Hypoxia-Inducible Factor 1 ; OSM protein, human ; OSMR protein, human ; Oncostatin M Receptor beta Subunit ; Reactive Oxygen Species ; Vascular Endothelial Growth Factor A ; vascular endothelial growth factor A, mouse ; Oncostatin M (106956-32-5) |
| Language | English |
| Publishing date | 2019-12-20 |
| Publishing country | Switzerland |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 2661518-6 |
| ISSN | 2073-4409 ; 2073-4409 |
| ISSN (online) | 2073-4409 |
| ISSN | 2073-4409 |
| DOI | 10.3390/cells9010028 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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