S Di Mauro1, M Ragusa2, F Urbano1, A Filippello1, A Di Pino1, A Scamporrino1, A Pulvirenti3, A Ferro3, A M Rabuazzo1, M Purrello2, F Purrello4, S Piro1. 1. Department of Clinical and Experimental Medicine, Internal Medicine, Garibaldi-Nesima Hospital, University of Catania, Catania, Italy. 2. Department of BioMedical Sciences and BioTechnology, Section of Biology and Genetics Giovanni Sichel, Unit of BioMolecular, Genome and Complex Systems BioMedicine, Catania, Italy. 3. Department of Clinical and Experimental Medicine, Bioinformatics, University of Catania, Catania, Italy. 4. Department of Clinical and Experimental Medicine, Internal Medicine, Garibaldi-Nesima Hospital, University of Catania, Catania, Italy. Electronic address: fpurrell@unict.it.
Abstract
BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) represents the most common chronic liver disease in industrialized countries. NAFLD has the potential to progress through the inflammatory phase of nonalcoholic steatohepatitis (NASH) to fibrosis, cirrhosis, and hepatocellular carcinoma. Identifying patients at risk for this transition is a relevant clinical challenge. The complexity of these phenotypes in vivo made necessary the development of in vitro models in order to dissect the molecular signalling affected in NAFLD and NASH, but also to identify potential circulating biomarkers. METHODS AND RESULTS: We profiled the expression of 754 cellular and medium-secreted human miRNAs in HepG2 cells after lipotoxic (Palmitate, model of NASH) or not-lipotoxic stimuli (Oleate-Palmitate, model of NAFLD). Results were validated through Single TaqMan assays. We performed computational analysis of miRNA targets and pathways. Oleate-palmitate treatment induced a variation of 2.8% and 10% of total miRNAs in cells and medium, respectively; palmitate treatment caused 10% and 19% intracellular and extracellular miRNA deregulation, respectively. We validated miR-126, miR-150, miR-223, miR-483-3p, miR-1226*, and miR-1290 deregulation. Through computational analysis, we observed that targets of both intracellular and extracellular DE miRNAs were involved in processes associated with the onset and progression of NAFLD and NASH, such as fatty acid metabolism, apoptosis and inflammation. CONCLUSIONS: These data would be useful to elucidate the role of miRNAs in the pathogenesis and progression of the NAFLD spectrum, but they also allow the identification of novel potential biomarkers for differential diagnosis to be tested in vivo. Copyright Â
BACKGROUND & AIMS:Nonalcoholic fatty liver disease (NAFLD) represents the most common chronic liver disease in industrialized countries. NAFLD has the potential to progress through the inflammatory phase of nonalcoholic steatohepatitis (NASH) to fibrosis, cirrhosis, and hepatocellular carcinoma. Identifying patients at risk for this transition is a relevant clinical challenge. The complexity of these phenotypes in vivo made necessary the development of in vitro models in order to dissect the molecular signalling affected in NAFLD and NASH, but also to identify potential circulating biomarkers. METHODS AND RESULTS: We profiled the expression of 754 cellular and medium-secreted human miRNAs in HepG2 cells after lipotoxic (Palmitate, model of NASH) or not-lipotoxic stimuli (Oleate-Palmitate, model of NAFLD). Results were validated through Single TaqMan assays. We performed computational analysis of miRNA targets and pathways. Oleate-palmitate treatment induced a variation of 2.8% and 10% of total miRNAs in cells and medium, respectively; palmitate treatment caused 10% and 19% intracellular and extracellular miRNA deregulation, respectively. We validated miR-126, miR-150, miR-223, miR-483-3p, miR-1226*, and miR-1290 deregulation. Through computational analysis, we observed that targets of both intracellular and extracellular DE miRNAs were involved in processes associated with the onset and progression of NAFLD and NASH, such as fatty acid metabolism, apoptosis and inflammation. CONCLUSIONS: These data would be useful to elucidate the role of miRNAs in the pathogenesis and progression of the NAFLD spectrum, but they also allow the identification of novel potential biomarkers for differential diagnosis to be tested in vivo. Copyright Â
Authors: Stefania Di Mauro; Alessandra Scamporrino; Salvatore Petta; Francesca Urbano; Agnese Filippello; Marco Ragusa; Maria T Di Martino; Francesca Scionti; Stefania Grimaudo; Rosaria M Pipitone; Graziella Privitera; Antonino Di Pino; Roberto Scicali; Luca Valenti; Paola Dongiovanni; Anna Fracanzani; Agata M Rabuazzo; Antonio Craxì; Michele Purrello; Francesco Purrello; Salvatore Piro Journal: Liver Int Date: 2019-06-26 Impact factor: 5.828