Oncostatin M, A Profibrogenic Mediator Overexpressed in Non-Alcoholic Fatty Liver Disease, Stimulates Migration of Hepatic Myofibroblasts

Beatrice Foglia, Salvatore Sutti, Dario Pedicini, Stefania Cannito, Claudia Bocca, Marina Maggiora, Maria Rosaria Bevacqua, Chiara Rosso, Elisabetta Bugianesi, Emanuele Albano, Erica Novo, Maurizio Parola

Research output: Contribution to journalArticle

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.

Original languageEnglish
JournalCells
Volume9
Issue number1
DOIs
Publication statusPublished - Dec 20 2019

Fingerprint Dive into the research topics of 'Oncostatin M, A Profibrogenic Mediator Overexpressed in Non-Alcoholic Fatty Liver Disease, Stimulates Migration of Hepatic Myofibroblasts'. Together they form a unique fingerprint.

  • Cite this

    Foglia, B., Sutti, S., Pedicini, D., Cannito, S., Bocca, C., Maggiora, M., Bevacqua, M. R., Rosso, C., Bugianesi, E., Albano, E., Novo, E., & Parola, M. (2019). Oncostatin M, A Profibrogenic Mediator Overexpressed in Non-Alcoholic Fatty Liver Disease, Stimulates Migration of Hepatic Myofibroblasts. Cells, 9(1). https://doi.org/10.3390/cells9010028