Our main research focus is hepatic stellate cells (HSCs), key players in the pathogenesis of liver fibrosis. HSCs are normally quiescent resident cells, storing Vitamin A in the liver and modulating extracellular matrix production. However, in response to different kinds of stimuli, HSCs may undergo activation and differentiate into a highly proliferative and myofibroblast-like cells. Lipid content is crucial factor in HSC physiology, in fact their lipogenic activity downregulates accordingly with Vitamin A content and progressive activation. The genetic polymorphism I148M of the patatin-like phospholipase domain-containing 3 (PNPLA3) is associated with hepatic steatosis and its progression to steatohepatitis (NASH), fibrosis and cancer. This gives HSCs pro-fibrogenic and pro-inflammatory properties, therefore is of interest understanding the molecular mechanisms behind PNPLA3 mutation to decipher future therapies. Moreover, transgenic mouse models for metabolic lipases are routinely used in our lab in order to test treatments against cholestatic and fatty liver -induced injuries, fibrosis and finally to protect against immune-metabolic alterations connected to liver disease.
Methods & Techniques
Flow cytometry; ELISA; immunohistochemistry; Western blot; cell culture; real time-PCR; lipid and molecular analysis; transgenic mouse models for NAFLD and cholestatic disorders
Tardelli M, Moreno-Viedma V, Zeyda M, Itariu BK, Langer FB, Prager G, Stulnig TM. Adiponectin regulates aquaglyceroporin expression in hepatic stellate cells altering their functional state. J Gastroenterol Hepatol 24: 226-230, 2016
Jürets A, Le Bras M, Staffler G, Stein G, Leitner L, Neuhofer A, Tardelli M, Turkof E, Zeyda M, Stulnig TM. Inhibition of cellular adhesion by immunological targeting of osteopontin neoepitopes generated through matrix metalloproteinase and thrombin Cceavage. PLoS One 11: e01483332016, 2016
Tardelli M, Zeyda K, Moreno-Viedma V, Wanko B, Grün NG, Staffler G, Zeyda M, Stulnig TM. Osteopontin is a key player for local adipose tissue macrophage proliferation in obesity. Mol Metab 5: 1131-1137, 2016
Bruschi FV, Claudel T, Tardelli M, Caligiuri A, Stulnig TM, Marra F, Trauner M. The PNPLA3 I148M variant modulates the fibrogenic phenotype of human hepatic stellate cells. Hepatology 65: 1875-1890, 2017
Tardelli M, Claudel T, Bruschi FV, Moreno-Viedma V, Trauner M. Adiponectin regulates AQP3 via PPARα in human hepatic stellate cells. Biochem Biophys Res Commun 490: 51-54, 2017