Lymphocytes as liver damage mirror of HCV related adipogenesis deregulation

Abstract

Hepatitis C virus infection leads to a wide spectrum of liver diseases ranging from mild chronic hepatitis to end-stage cirrhosis and hepatocellular carcinoma. An intriguing aspect of the HCV infection is its close connection with lipid metabolism playing an important role in the HCV life cycle and in its pathogenesis. HCV is known to be a hepatotropic virus; however, it can also infect peripheral blood mononuclear cells (PBMCs). The goal of the current investigation is to compare the adipogenesis profile of liver tissues to lymphocytes of HCV infected patients, in order to understand if PBMCs may reflect the alterations of intracellular pathways occurring during HCV-related liver steatosis. Using the Human Adipogenesis PCR Array, gene expression was analyzed in liver samples and PBMCs of chronic HCV+, HBV+ and Healthy Donors (HDs) patients. We observed a similar modulation of lipid metabolism in HCV+ and HBV+liver tissues and lymphoid, cells suggesting that PBMCs reflect the liver adipogenesis deregulation related to infection, even if the two viruses have a different impact in the regulation of the adipogenesis mechanisms. In particular, some genes involved in lipid metabolism and inflammation, as well as in cell transformation, were up-regulated, in a similar way, in both HCV models analyzed. Interestingly, these genes were positively correlated to virological and hepatic functional parameters of HCV+ patients. On the contrary, HBV+ patients displayed a completely different profile. PBMCs of HCV+ patients seem to be useful model to study how HCV-related lipid metabolism deregulation occurs in liver. The obtained data suggest some molecules as new possible biomarkers of HCV-related liver damage progression.

Small heterodimer partner 1 directly interacts with NS5A viral protein and has a key role in HCV related liver cell transformation

“…Our previously published data indicated that HCV infected patients were characterized by a deep deregulation of some genes involved in the control of lipid metabolism. Accordingly, we demonstrated that this feature was restricted to Hepatitis C virus infection, whereas HBV patients had different features [ 19 ]. Among all, the previously analyzed steatogenic genes (i.e.…”

“…Liver steatosis and oxidative stress play an important role in liver damage during HCV infection; accordingly, several transcriptional regulators of cholesterol and fatty acid metabolism have been shown to be implicated in HCV infection [ 22 – 23 ]. In a recent work, we investigated the expression profiles of genes associated to HCV-related steatogenesis in liver biopsies and PBMCs of HCV positive patients [ 19 ]. We highlighted the involvement of different Nuclear Receptor in this phenomenon, such as FXR, LXRs, HNF4.…”

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“…Human PBMCs from HDs were obtained from 17 individuals attending the local blood transfusion unit of Policlinico 'Tor Vergata' in Rome 31 . PBMCs were separated as previously described 59 . Cell lines and PBMCs were cultured at 37°C in a 5% CO 2 humidified atmosphere in the presence or absence of treatment.…”

Update on implications and mechanisms of angiogenesis in liver fibrosis

“…Recruitment of inflammatory cells takes place following injury, such as Kupffer cells (KC), leukocytes, lymphocytes, natural killer cells (NK), and so on. Some of these inflammatory cells can produce compounds that modulate HSC behavior.…”