Label-free mass spectrometry-based differential proteome of secreted proteins following interferon-alpha treatment of differentiated liver progenitor cells

摘要

Liver diseases are a major public health concern worldwide. In particular, patients infected with hepatitis viruses are at risk to develop cirrhosis and hepatocellular carcinoma (HCC). Interferon-(alpha) (IFN-(alpha)), a host cytokine produced in response to viral infections has antiviral, immunomodulatory and anticancer effects. IFN-(alpha) is the treatment of choice against viral hepatitis infections, and there is increasing evidence that it may be of potential benefit in the prevention of cirrhosis and HCC. The molecular mechanisms that underlie IFN-(alpha)-induced hepatitis virus inhibition, prevention of cirrhosis and HCC are not well understood. In particular, little is known on the IFN-induced secreted factors that may act by an autocrine loop or in a paracrine manner. A quantitative proteomic approach is most appropriate in revealing such changes. In this study, a labeling-free, quantitative proteomic technology was employed in determining proteins isolated from the supernatant of untreated and IFN-(alpha)-treated human HepaRG cells, that are hepatocytic progenitor cells capable of reaching morphological and biochemical levels of differentiation close to those of normal hepatocytes. Results are further compared with those obtained with a labeling quantitative method based on the SILAC (Stable Isotopic Labeling by Amino Acids in Cell Culture) approach.